Mutagenetix > Incidental Mutation

Incidental Mutation 'R7128:Wt1'

552436

Institutional Source

Beutler Lab

Gene Symbol

Wt1

Ensembl Gene

ENSMUSG00000016458

Gene Name

Wilms tumor 1 homolog

Synonyms

Wt-1, D630046I19Rik

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7128 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

105126529-105173616 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 105127325 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Histidine at position 177 (Y177H)

Ref Sequence

ENSEMBL: ENSMUSP00000117891 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000111098] [ENSMUST00000111099] [ENSMUST00000133470] [ENSMUST00000143043] [ENSMUST00000146842] [ENSMUST00000213301]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000111098

SMART Domains

Protein: ENSMUSP00000106727
Gene: ENSMUSG00000016458

Domain	Start	End	E-Value	Type
Pfam:WT1	1	160	5e-93	PFAM
ZnF_C2H2	162	186	1.33e-1	SMART
ZnF_C2H2	192	216	2.12e-4	SMART
ZnF_C2H2	222	244	1.92e-2	SMART
ZnF_C2H2	253	277	1.89e-1	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000111099

SMART Domains

Protein: ENSMUSP00000106728
Gene: ENSMUSG00000016458

Domain	Start	End	E-Value	Type
Pfam:WT1	1	119	6.2e-63	PFAM
Pfam:WT1	113	177	4.6e-27	PFAM
ZnF_C2H2	179	203	1.33e-1	SMART
ZnF_C2H2	209	233	2.12e-4	SMART
ZnF_C2H2	239	261	1.92e-2	SMART
ZnF_C2H2	267	291	1.89e-1	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000133470
AA Change: Y109H

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000120054
Gene: ENSMUSG00000016458
AA Change: Y109H

Domain	Start	End	E-Value	Type
Pfam:WT1	1	304	3.2e-165	PFAM
ZnF_C2H2	306	330	1.33e-1	SMART
ZnF_C2H2	336	360	2.12e-4	SMART
ZnF_C2H2	366	388	1.92e-2	SMART

Predicted Effect

SMART Domains

Protein: ENSMUSP00000123592
Gene: ENSMUSG00000016458
AA Change: Y39H

Domain	Start	End	E-Value	Type
Pfam:WT1	1	235	9.8e-135	PFAM
ZnF_C2H2	237	261	1.33e-1	SMART
ZnF_C2H2	267	291	2.12e-4	SMART
ZnF_C2H2	297	319	1.92e-2	SMART
ZnF_C2H2	325	349	1.89e-1	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000143043
AA Change: Y177H

PolyPhen 2 Score 0.035 (Sensitivity: 0.94; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000117891
Gene: ENSMUSG00000016458
AA Change: Y177H

Domain	Start	End	E-Value	Type
Pfam:WT1	69	389	1e-149	PFAM
ZnF_C2H2	391	415	1.33e-1	SMART
ZnF_C2H2	421	445	2.12e-4	SMART
ZnF_C2H2	451	473	1.92e-2	SMART
ZnF_C2H2	482	506	1.89e-1	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000146842
AA Change: Y109H

PolyPhen 2 Score 0.057 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000120702
Gene: ENSMUSG00000016458
AA Change: Y109H

Domain	Start	End	E-Value	Type
Pfam:WT1	1	225	5.1e-117	PFAM
Pfam:WT1	222	278	2.1e-26	PFAM
ZnF_C2H2	280	304	1.33e-1	SMART
ZnF_C2H2	310	334	2.12e-4	SMART
ZnF_C2H2	340	362	1.92e-2	SMART
ZnF_C2H2	371	395	1.89e-1	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000213301
AA Change: Y177H

PolyPhen 2 Score 0.126 (Sensitivity: 0.93; Specificity: 0.86)

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.0%

Validation Efficiency

MGI Phenotype

FUNCTION: This gene encodes a transcription factor that contains four zinc-finger motifs at the C-terminus and a proline/glutamine-rich DNA-binding domain at the N-terminus. It plays an essential role in the normal development of the urogenital system, and the orthologous human gene is mutated in a small subset of patients with Wilm's tumors. Alternative splicing has been noted for this gene, however, the full-length nature of these variants is not known. The mRNA for this gene has been shown to initiate translation from non-AUG (CUG) and AUG translation start sites, resulting in different isoforms. [provided by RefSeq, Apr 2013]
PHENOTYPE: Homozygous mutants fail to develop normal kidneys or gonads, and on some genetic backgrounds, a spleen. Mutants have abnormalities of the heart, mesothelium and lungs and die between embryonic day 13.5 and birth. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 68 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
9930021J03Rik	T	C	19: 29,716,481	T1871A	possibly damaging	Het
Adgb	T	C	10: 10,472,241	D25G	probably benign	Het
Ak9	T	C	10: 41,424,717	V1641A	unknown	Het
Akap2	T	C	4: 57,855,816	S382P	probably benign	Het
Akirin2	T	C	4: 34,562,435	I118T	probably benign	Het
Aldh1l1	G	T	6: 90,563,379	Q215H	probably benign	Het
Arhgef26	T	C	3: 62,419,550	F495L	possibly damaging	Het
Atg4a-ps	T	A	3: 103,645,747	R93*	probably null	Het
AW822073	T	C	10: 58,223,657	Q425R	unknown	Het
Catsper3	A	G	13: 55,798,849	I120V	probably benign	Het
Cavin2	A	G	1: 51,289,420	Q12R	possibly damaging	Het
Cenpf	A	T	1: 189,684,991	F39Y	probably damaging	Het
Chfr	T	C	5: 110,143,636	Y107H	probably benign	Het
Cmtm1	CGGCACGTACTGAAGGTCGCTGACTGGATGGTGTGGCACGTACTGAAGGTCGCTGACTGGATGGTGTGGCACGTACTGAAGGTCGCTGACTGGATGGT	CGGCACGTACTGAAGGTCGCTGACTGGATGGTGTGGCACGTACTGAAGGTCGCTGACTGGATGGT	8: 104,309,470		probably benign	Het
Defb4	T	A	8: 19,201,204	I29K	possibly damaging	Het
Dnah7c	A	G	1: 46,527,485	T619A	probably benign	Het
Emc3	A	G	6: 113,517,920	L179P	probably damaging	Het
Eno3	G	C	11: 70,658,604	V84L	possibly damaging	Het
Fam110a	C	T	2: 151,970,722	V43M	probably damaging	Het
Fam159a	G	T	4: 108,367,903	T154K	probably benign	Het
Fbxo30	T	A	10: 11,290,116	L194*	probably null	Het
Galnt14	T	C	17: 73,545,101	T108A	probably benign	Het
Glipr2	T	C	4: 43,968,601	I51T	probably benign	Het
Gm1527	C	T	3: 28,915,311	S270F	possibly damaging	Het
Gm3336	A	G	8: 70,718,554	M1V	probably null	Het
Gm4744	T	C	6: 40,950,376	D15G		Het
Gm4763	C	T	7: 24,725,999		probably null	Het
Gm4924	G	A	10: 82,378,699	C777Y	unknown	Het
Gm5901	G	A	7: 105,378,201	G306S	probably damaging	Het
Gon4l	T	A	3: 88,895,692	N1203K	possibly damaging	Het
Gpr161	A	T	1: 165,310,457	Y204F	possibly damaging	Het
Igsf10	T	C	3: 59,328,905	E1285G	probably benign	Het
Irx6	T	C	8: 92,677,366	L187P	probably damaging	Het
Itgb1bp1	A	G	12: 21,272,088	Y117H	probably benign	Het
Itln1	C	A	1: 171,530,575	D202Y	possibly damaging	Het
Kctd9	T	C	14: 67,738,523	S242P	probably benign	Het
Lrrk2	A	G	15: 91,801,885	H2143R	probably benign	Het
Lynx1	G	A	15: 74,751,549	R50*	probably null	Het
Map10	A	G	8: 125,671,853	I662V	probably benign	Het
Mlxipl	T	C	5: 135,133,851	L691P	probably damaging	Het
Muc16	A	G	9: 18,643,004	S3998P	unknown	Het
Nalcn	A	T	14: 123,594,502	V120E	probably damaging	Het
Nfat5	T	C	8: 107,358,691	S539P	probably benign	Het
Olfml3	T	C	3: 103,737,168	M62V	probably benign	Het
Orm3	T	C	4: 63,357,825	V158A	probably benign	Het
Pced1b	A	T	15: 97,384,598	K173*	probably null	Het
Pdzd7	T	C	19: 45,027,949	D911G	probably damaging	Het
Pkn3	A	G	2: 30,083,315	D383G	probably damaging	Het
Pm20d1	A	G	1: 131,797,554	E46G	probably benign	Het
Pyroxd2	A	T	19: 42,731,403	S455T	probably benign	Het
Rmnd5b	T	A	11: 51,624,537	I301F	possibly damaging	Het
Rnf225	A	G	7: 12,927,984	N30S	probably benign	Het
Slfn3	T	A	11: 83,214,895	C573S	probably benign	Het
Smc6	A	G	12: 11,301,631	E887G	probably damaging	Het
Sp140	A	T	1: 85,620,125	D191V	possibly damaging	Het
Srf	C	T	17: 46,555,446	S128N	possibly damaging	Het
Sult6b1	T	C	17: 78,894,641	D144G	probably damaging	Het
Syne1	G	A	10: 5,243,180	A3956V	probably damaging	Het
Syt10	A	T	15: 89,814,111	D343E	probably damaging	Het
Tgtp2	G	A	11: 49,059,308	R146C	possibly damaging	Het
Tmcc3	A	T	10: 94,430,634		probably benign	Het
Tnfrsf1a	A	T	6: 125,361,536	T337S	probably benign	Het
Tns1	A	T	1: 73,995,304	I144N		Het
Trim11	A	G	11: 58,978,277	E13G	probably damaging	Het
Trpm6	A	T	19: 18,811,773	H569L	possibly damaging	Het
Ttbk2	T	A	2: 120,746,088	I803L	probably benign	Het
Vmn1r21	G	T	6: 57,843,951	N169K	probably damaging	Het
Vmn2r60	C	T	7: 42,195,112	T633I	probably damaging	Het

Other mutations in Wt1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00434:Wt1	APN	2	105144141	critical splice acceptor site	probably null
IGL00846:Wt1	APN	2	105166957	missense	probably damaging	1.00
IGL01411:Wt1	APN	2	105132974	missense	probably damaging	1.00
IGL02936:Wt1	APN	2	105169039	missense	probably damaging	1.00
IGL03063:Wt1	APN	2	105170023	splice site	probably null
R0127:Wt1	UTSW	2	105133457	missense	probably damaging	1.00
R1462:Wt1	UTSW	2	105166831	missense	probably damaging	1.00
R1462:Wt1	UTSW	2	105166831	missense	probably damaging	1.00
R2061:Wt1	UTSW	2	105131157	splice site	probably null
R2284:Wt1	UTSW	2	105172321	missense	probably benign	0.43
R2358:Wt1	UTSW	2	105163428	splice site	probably benign
R3711:Wt1	UTSW	2	105163428	splice site	probably benign
R5096:Wt1	UTSW	2	105143125	missense	probably damaging	1.00
R5590:Wt1	UTSW	2	105127284	missense	probably damaging	1.00
R5984:Wt1	UTSW	2	105172252	missense	probably benign	0.44
R6821:Wt1	UTSW	2	105172267	missense	probably damaging	1.00
R7698:Wt1	UTSW	2	105126816	missense	probably benign	0.33
R7913:Wt1	UTSW	2	105166860	missense	probably damaging	0.98
R8005:Wt1	UTSW	2	105127444	critical splice donor site	probably null
R8944:Wt1	UTSW	2	105127239	missense	possibly damaging	0.92
R9032:Wt1	UTSW	2	105126815	missense	probably benign	0.18
R9569:Wt1	UTSW	2	105163366	missense	possibly damaging	0.93
Z1176:Wt1	UTSW	2	105127107	missense	probably damaging	0.98

Predicted Primers

PCR Primer
(F):5'- AAGTCCAGCGCCGAGAATC -3'
(R):5'- GCTGCTGAGTAAGAACTGGC -3'

Sequencing Primer
(F):5'- TCATGGGTTCCGACGTGC -3'
(R):5'- CTGCTGAGTAAGAACTGGCATCAG -3'

Posted On

2019-05-15