Mutagenetix > Incidental Mutation

Incidental Mutation 'R2112:Ambra1'

232630

Institutional Source

Beutler Lab

Gene Symbol

Ambra1

Ensembl Gene

ENSMUSG00000040506

Gene Name

autophagy/beclin 1 regulator 1

Synonyms

2310079H06Rik, D030051N19Rik

MMRRC Submission

040116-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.905) question?

Stock #

R2112 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

91560479-91749194 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 91706132 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tryptophan to Arginine at position 746 (W746R)

Ref Sequence

ENSEMBL: ENSMUSP00000106949 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000045699] [ENSMUST00000045705] [ENSMUST00000099712] [ENSMUST00000111316] [ENSMUST00000111317]

AlphaFold

A2AH22

Predicted Effect

probably damaging
Transcript: ENSMUST00000045699
AA Change: W746R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000048898
Gene: ENSMUSG00000040506
AA Change: W746R

Domain	Start	End	E-Value	Type
WD40	50	81	4.11e1	SMART
WD40	84	124	1.16e-9	SMART
WD40	126	164	1.19e0	SMART
low complexity region	351	361	N/A	INTRINSIC
low complexity region	393	404	N/A	INTRINSIC
low complexity region	538	554	N/A	INTRINSIC
low complexity region	591	603	N/A	INTRINSIC
low complexity region	636	643	N/A	INTRINSIC
Blast:WD40	812	850	1e-5	BLAST
Blast:WD40	871	918	1e-7	BLAST
low complexity region	942	954	N/A	INTRINSIC
low complexity region	1002	1026	N/A	INTRINSIC
low complexity region	1127	1143	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000045705
AA Change: W866R

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000049258
Gene: ENSMUSG00000040506
AA Change: W866R

Domain	Start	End	E-Value	Type
WD40	50	81	4.11e1	SMART
WD40	84	124	1.16e-9	SMART
WD40	126	164	1.19e0	SMART
low complexity region	267	285	N/A	INTRINSIC
low complexity region	442	452	N/A	INTRINSIC
low complexity region	484	495	N/A	INTRINSIC
low complexity region	629	645	N/A	INTRINSIC
low complexity region	682	704	N/A	INTRINSIC
low complexity region	756	763	N/A	INTRINSIC
Blast:WD40	932	970	1e-5	BLAST
Blast:WD40	991	1038	1e-7	BLAST
low complexity region	1062	1074	N/A	INTRINSIC
low complexity region	1122	1146	N/A	INTRINSIC
low complexity region	1247	1263	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000099712
AA Change: W775R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000097299
Gene: ENSMUSG00000040506
AA Change: W775R

Domain	Start	End	E-Value	Type
WD40	50	81	4.11e1	SMART
WD40	84	124	1.16e-9	SMART
WD40	126	164	1.19e0	SMART
low complexity region	351	361	N/A	INTRINSIC
low complexity region	393	404	N/A	INTRINSIC
low complexity region	538	554	N/A	INTRINSIC
low complexity region	591	613	N/A	INTRINSIC
low complexity region	665	672	N/A	INTRINSIC
Blast:WD40	841	879	1e-5	BLAST
Blast:WD40	900	947	1e-7	BLAST
low complexity region	971	983	N/A	INTRINSIC
low complexity region	1031	1055	N/A	INTRINSIC
low complexity region	1156	1172	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000111316
AA Change: W806R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000106948
Gene: ENSMUSG00000040506
AA Change: W806R

Domain	Start	End	E-Value	Type
WD40	50	81	4.11e1	SMART
WD40	84	124	1.16e-9	SMART
WD40	126	164	1.19e0	SMART
low complexity region	267	285	N/A	INTRINSIC
low complexity region	442	452	N/A	INTRINSIC
low complexity region	484	495	N/A	INTRINSIC
low complexity region	629	645	N/A	INTRINSIC
low complexity region	682	704	N/A	INTRINSIC
Blast:WD40	872	910	1e-5	BLAST
Blast:WD40	931	978	1e-7	BLAST
low complexity region	1002	1014	N/A	INTRINSIC
low complexity region	1062	1086	N/A	INTRINSIC
low complexity region	1187	1203	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000111317
AA Change: W746R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000106949
Gene: ENSMUSG00000040506
AA Change: W746R

Domain	Start	End	E-Value	Type
WD40	50	81	4.11e1	SMART
WD40	84	124	1.16e-9	SMART
WD40	126	164	1.19e0	SMART
low complexity region	351	361	N/A	INTRINSIC
low complexity region	393	404	N/A	INTRINSIC
low complexity region	538	554	N/A	INTRINSIC
low complexity region	591	603	N/A	INTRINSIC
low complexity region	636	643	N/A	INTRINSIC
Blast:WD40	812	850	1e-5	BLAST
Blast:WD40	871	918	1e-7	BLAST
low complexity region	942	954	N/A	INTRINSIC
low complexity region	1002	1026	N/A	INTRINSIC
low complexity region	1127	1143	N/A	INTRINSIC

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.3%
20x: 95.1%

Validation Efficiency

MGI Phenotype

PHENOTYPE: Most mice homozygous for a gene trap mutation die at E10-E14.5 with severe neural tube defects manifest as midbrain/hindbrain exencephaly and/or spina bifida and associated with impaired autophagy, accumulation of ubiquitinated proteins, abnormal cell proliferation and excessive apoptosis. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 94 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam1b	A	G	5: 121,638,777 (GRCm39)		probably benign	Het
Adprhl1	A	G	8: 13,298,694 (GRCm39)	Y79H	probably damaging	Het
Ankhd1	A	T	18: 36,774,679 (GRCm39)	K1420I	probably damaging	Het
Ap1b1	T	C	11: 4,965,613 (GRCm39)	F51L	probably damaging	Het
Arhgap24	A	C	5: 103,040,366 (GRCm39)	R434S	probably damaging	Het
Arhgap29	T	C	3: 121,805,210 (GRCm39)	L525P	probably benign	Het
Arpc1b	T	C	5: 145,060,579 (GRCm39)	Y124H	probably damaging	Het
Arr3	T	A	X: 99,658,247 (GRCm39)	F269L	possibly damaging	Het
Atp11b	G	T	3: 35,891,677 (GRCm39)	V830F	probably damaging	Het
Ccdc71l	T	A	12: 32,429,229 (GRCm39)	F83I	probably damaging	Het
Cdh23	G	T	10: 60,141,362 (GRCm39)	F3127L	probably damaging	Het
Cfap251	G	A	5: 123,392,438 (GRCm39)		probably benign	Het
Cldn15	T	A	5: 136,997,016 (GRCm39)	M19K	possibly damaging	Het
Cog4	A	G	8: 111,585,214 (GRCm39)	Y292C	possibly damaging	Het
Col12a1	A	G	9: 79,551,181 (GRCm39)	V2145A	possibly damaging	Het
Col5a3	T	C	9: 20,721,073 (GRCm39)	I110V	unknown	Het
Cps1	T	A	1: 67,216,139 (GRCm39)	D821E	probably benign	Het
Crnkl1	A	T	2: 145,772,617 (GRCm39)	Y153*	probably null	Het
Dock10	T	A	1: 80,483,359 (GRCm39)	K2082M	probably damaging	Het
Dock10	T	C	1: 80,483,360 (GRCm39)	K2083E	probably damaging	Het
Dst	T	C	1: 34,208,259 (GRCm39)	S737P	probably damaging	Het
Dthd1	T	C	5: 62,979,251 (GRCm39)	Y304H	probably damaging	Het
Dthd1	T	C	5: 63,000,222 (GRCm39)	S515P	probably damaging	Het
Etf1	A	T	18: 35,042,154 (GRCm39)		probably null	Het
Fmnl2	A	G	2: 52,995,549 (GRCm39)	E424G	probably damaging	Het
Galt	A	G	4: 41,758,245 (GRCm39)	T337A	probably benign	Het
Gbp4	A	G	5: 105,283,042 (GRCm39)	L76P	possibly damaging	Het
Gcfc2	C	A	6: 81,900,759 (GRCm39)	D24E	probably benign	Het
Gigyf2	A	G	1: 87,368,452 (GRCm39)	H1044R	probably damaging	Het
Glg1	T	C	8: 111,919,178 (GRCm39)	D315G	probably damaging	Het
Gm4787	C	T	12: 81,424,607 (GRCm39)	C517Y	probably damaging	Het
Gnl3l	A	G	X: 149,780,290 (GRCm39)	S217P	probably damaging	Het
Gpr37	T	C	6: 25,669,380 (GRCm39)	Y488C	possibly damaging	Het
Hap1	T	C	11: 100,244,825 (GRCm39)	D240G	probably benign	Het
Hhla1	C	G	15: 65,808,232 (GRCm39)	W271S	probably benign	Het
Hmgxb3	T	C	18: 61,288,458 (GRCm39)	R470G	possibly damaging	Het
Inpp5a	A	G	7: 139,154,877 (GRCm39)	D332G	probably damaging	Het
Insr	A	G	8: 3,219,748 (GRCm39)	S925P	probably benign	Het
Isoc2b	T	A	7: 4,852,474 (GRCm39)	D171V	probably damaging	Het
Kif20b	T	C	19: 34,909,132 (GRCm39)	I223T	probably benign	Het
Krt6b	T	C	15: 101,586,999 (GRCm39)	T258A	possibly damaging	Het
Lipo4	G	A	19: 33,488,926 (GRCm39)	P219L	probably benign	Het
Luc7l	T	C	17: 26,474,101 (GRCm39)		probably null	Het
Madd	T	C	2: 91,007,321 (GRCm39)	K264E	possibly damaging	Het
Mcf2l	A	T	8: 13,051,867 (GRCm39)	K433N	probably damaging	Het
Mob3b	A	T	4: 35,083,795 (GRCm39)	N131K	probably damaging	Het
Mtus1	G	T	8: 41,475,608 (GRCm39)	P819T	probably damaging	Het
Myo15a	T	C	11: 60,384,994 (GRCm39)	F1699L	probably damaging	Het
Nav1	C	T	1: 135,376,742 (GRCm39)	R1694Q	probably damaging	Het
Neb	G	C	2: 52,218,776 (GRCm39)	T78S	probably damaging	Het
Nek2	T	C	1: 191,559,320 (GRCm39)	V275A	probably benign	Het
Nfatc1	A	T	18: 80,678,879 (GRCm39)	C836*	probably null	Het
Nos1	T	C	5: 118,074,636 (GRCm39)	V1060A	probably benign	Het
Notch3	T	A	17: 32,363,584 (GRCm39)	I1160F	probably benign	Het
Nox4	T	C	7: 87,021,216 (GRCm39)	L476P	probably damaging	Het
Npc1	A	T	18: 12,346,529 (GRCm39)	N222K	possibly damaging	Het
Nrn1l	C	A	8: 106,621,378 (GRCm39)	H109Q	possibly damaging	Het
Or4c11	T	C	2: 88,695,545 (GRCm39)	S199P	possibly damaging	Het
Or4k15	G	T	14: 50,364,080 (GRCm39)	L15F	probably damaging	Het
Or6d13	T	C	6: 116,517,611 (GRCm39)	Y66H	possibly damaging	Het
Or7a41	T	C	10: 78,871,248 (GRCm39)	L206P	probably damaging	Het
Or8g27	T	C	9: 39,129,075 (GRCm39)	Y141H	probably benign	Het
Or8g33	C	A	9: 39,337,966 (GRCm39)	V134L	probably benign	Het
Pcnt	T	C	10: 76,256,360 (GRCm39)	K627E	probably damaging	Het
Plch1	T	A	3: 63,630,227 (GRCm39)	T514S	probably damaging	Het
Ppargc1b	G	A	18: 61,444,321 (GRCm39)	P297S	probably benign	Het
Ppig	A	G	2: 69,580,451 (GRCm39)	T662A	unknown	Het
Prdm2	A	C	4: 142,858,506 (GRCm39)	S1595A	probably benign	Het
Ptpn5	T	A	7: 46,732,890 (GRCm39)	T318S	probably benign	Het
Ralgps2	A	G	1: 156,660,278 (GRCm39)	Y265H	probably damaging	Het
Seh1l	T	C	18: 67,920,249 (GRCm39)	I182T	probably damaging	Het
Slc12a6	T	C	2: 112,186,830 (GRCm39)	I943T	probably damaging	Het
Slc5a5	A	T	8: 71,342,395 (GRCm39)		probably null	Het
Sparcl1	T	A	5: 104,236,289 (GRCm39)	Q488L	probably damaging	Het
Sphkap	T	G	1: 83,253,602 (GRCm39)	K1382N	probably benign	Het
Sybu	T	C	15: 44,536,731 (GRCm39)	S532G	probably benign	Het
Syde2	G	A	3: 145,704,241 (GRCm39)	G131S	possibly damaging	Het
Taok1	C	T	11: 77,462,472 (GRCm39)	V206I	probably benign	Het
Tas1r2	G	T	4: 139,382,666 (GRCm39)	M101I	probably benign	Het
Trpc6	C	T	9: 8,656,613 (GRCm39)	T680I	probably damaging	Het
Trub1	T	C	19: 57,473,646 (GRCm39)		probably null	Het
Tspan1	G	T	4: 116,020,885 (GRCm39)		probably null	Het
Ttc28	G	A	5: 111,424,139 (GRCm39)	E1438K	probably damaging	Het
Ubr3	A	G	2: 69,808,136 (GRCm39)	T1206A	possibly damaging	Het
Ulbp3	C	T	10: 3,076,459 (GRCm39)		noncoding transcript	Het
Usp40	A	G	1: 87,877,936 (GRCm39)	I1117T	probably benign	Het
Usp43	G	T	11: 67,812,536 (GRCm39)	N113K	probably damaging	Het
Vcan	T	A	13: 89,841,422 (GRCm39)	D414V	probably damaging	Het
Vmn1r202	T	A	13: 22,685,904 (GRCm39)	Y171F	possibly damaging	Het
Zfp142	A	G	1: 74,612,795 (GRCm39)	S451P	probably damaging	Het
Zfp516	A	G	18: 82,975,536 (GRCm39)	D578G	probably damaging	Het
Zfp90	G	A	8: 107,152,120 (GRCm39)	C611Y	probably damaging	Het
Zfp954	A	G	7: 7,118,609 (GRCm39)	C312R	probably damaging	Het
Zmym3	A	T	X: 100,450,993 (GRCm39)	V1208D	probably damaging	Het

Other mutations in Ambra1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00264:Ambra1	APN	2	91,741,934 (GRCm39)	missense	probably benign	0.01
IGL00861:Ambra1	APN	2	91,601,271 (GRCm39)	missense	possibly damaging	0.81
IGL00911:Ambra1	APN	2	91,598,027 (GRCm39)	splice site	probably benign
IGL01371:Ambra1	APN	2	91,655,631 (GRCm39)	missense	probably damaging	1.00
IGL01532:Ambra1	APN	2	91,715,977 (GRCm39)	missense	probably damaging	1.00
IGL01620:Ambra1	APN	2	91,741,757 (GRCm39)	critical splice acceptor site	probably null
IGL02147:Ambra1	APN	2	91,598,064 (GRCm39)	missense	probably benign	0.01
IGL02170:Ambra1	APN	2	91,597,432 (GRCm39)	missense	possibly damaging	0.66
IGL02173:Ambra1	APN	2	91,748,013 (GRCm39)	missense	probably benign
IGL02212:Ambra1	APN	2	91,747,706 (GRCm39)	missense	probably damaging	1.00
IGL02256:Ambra1	APN	2	91,599,399 (GRCm39)	missense	possibly damaging	0.95
IGL02319:Ambra1	APN	2	91,717,265 (GRCm39)	missense	probably damaging	1.00
IGL02502:Ambra1	APN	2	91,730,877 (GRCm39)	missense	probably damaging	1.00
IGL02961:Ambra1	APN	2	91,741,793 (GRCm39)	missense	possibly damaging	0.86
R0003:Ambra1	UTSW	2	91,741,773 (GRCm39)	missense	probably damaging	1.00
R0098:Ambra1	UTSW	2	91,598,056 (GRCm39)	missense	possibly damaging	0.66
R0173:Ambra1	UTSW	2	91,640,564 (GRCm39)	splice site	probably benign
R0414:Ambra1	UTSW	2	91,706,084 (GRCm39)	missense	possibly damaging	0.84
R0579:Ambra1	UTSW	2	91,654,810 (GRCm39)	missense	possibly damaging	0.66
R1212:Ambra1	UTSW	2	91,599,381 (GRCm39)	missense	possibly damaging	0.94
R1241:Ambra1	UTSW	2	91,601,241 (GRCm39)	splice site	probably benign
R1467:Ambra1	UTSW	2	91,716,048 (GRCm39)	missense	probably damaging	1.00
R1467:Ambra1	UTSW	2	91,716,048 (GRCm39)	missense	probably damaging	1.00
R1533:Ambra1	UTSW	2	91,717,210 (GRCm39)	missense	probably damaging	1.00
R1916:Ambra1	UTSW	2	91,741,806 (GRCm39)	missense	probably damaging	1.00
R2080:Ambra1	UTSW	2	91,716,064 (GRCm39)	missense	probably damaging	1.00
R2083:Ambra1	UTSW	2	91,596,945 (GRCm39)	missense	possibly damaging	0.83
R2255:Ambra1	UTSW	2	91,747,806 (GRCm39)	missense	probably damaging	1.00
R3407:Ambra1	UTSW	2	91,740,652 (GRCm39)	missense	probably damaging	1.00
R3732:Ambra1	UTSW	2	91,640,476 (GRCm39)	missense	probably damaging	1.00
R4111:Ambra1	UTSW	2	91,730,903 (GRCm39)	missense	probably damaging	1.00
R4792:Ambra1	UTSW	2	91,603,191 (GRCm39)	missense	possibly damaging	0.66
R4879:Ambra1	UTSW	2	91,603,039 (GRCm39)	intron	probably benign
R5007:Ambra1	UTSW	2	91,602,655 (GRCm39)	missense	possibly damaging	0.79
R5261:Ambra1	UTSW	2	91,715,951 (GRCm39)	missense	probably damaging	1.00
R6141:Ambra1	UTSW	2	91,706,099 (GRCm39)	missense	probably damaging	1.00
R6364:Ambra1	UTSW	2	91,603,661 (GRCm39)	missense	possibly damaging	0.66
R6413:Ambra1	UTSW	2	91,599,429 (GRCm39)	missense	possibly damaging	0.92
R6868:Ambra1	UTSW	2	91,747,878 (GRCm39)	missense	possibly damaging	0.83
R6888:Ambra1	UTSW	2	91,599,372 (GRCm39)	missense	probably damaging	1.00
R6964:Ambra1	UTSW	2	91,747,761 (GRCm39)	nonsense	probably null
R6970:Ambra1	UTSW	2	91,602,945 (GRCm39)	intron	probably benign
R6982:Ambra1	UTSW	2	91,747,818 (GRCm39)	missense	probably damaging	1.00
R7205:Ambra1	UTSW	2	91,598,103 (GRCm39)	missense	possibly damaging	0.46
R7458:Ambra1	UTSW	2	91,748,029 (GRCm39)	missense	probably benign	0.26
R7786:Ambra1	UTSW	2	91,598,141 (GRCm39)	missense	possibly damaging	0.46
R7812:Ambra1	UTSW	2	91,596,911 (GRCm39)	start codon destroyed	probably benign	0.00
R7825:Ambra1	UTSW	2	91,598,106 (GRCm39)	missense	probably damaging	1.00
R7860:Ambra1	UTSW	2	91,603,838 (GRCm39)	missense	probably benign	0.27
R8190:Ambra1	UTSW	2	91,602,697 (GRCm39)	missense	possibly damaging	0.95
R8779:Ambra1	UTSW	2	91,747,719 (GRCm39)	missense	probably benign	0.05
R9044:Ambra1	UTSW	2	91,740,434 (GRCm39)	intron	probably benign
R9062:Ambra1	UTSW	2	91,740,662 (GRCm39)	missense	possibly damaging	0.82
R9707:Ambra1	UTSW	2	91,640,476 (GRCm39)	missense	probably damaging	1.00
Z1177:Ambra1	UTSW	2	91,730,953 (GRCm39)	missense	possibly damaging	0.82
Z1177:Ambra1	UTSW	2	91,706,131 (GRCm39)	missense	probably damaging	0.97
Z1177:Ambra1	UTSW	2	91,599,344 (GRCm39)	missense	possibly damaging	0.81

Predicted Primers

PCR Primer
(F):5'- TGCAGTGACTTGCCATGTGG -3'
(R):5'- AAATGTGTTACTGGTAGCTGAGGC -3'

Sequencing Primer
(F):5'- CAGTGACTTGCCATGTGGATCTC -3'
(R):5'- CTAAGCATACAGAAATAGTGCATGAC -3'

Posted On

2014-09-18