Mutagenetix > Incidental Mutation

Incidental Mutation 'R8110:Mettl3'

630828

Institutional Source

Beutler Lab

Gene Symbol

Mettl3

Ensembl Gene

ENSMUSG00000022160

Gene Name

methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit

Synonyms

M6A, 2310024F18Rik, Spo8

MMRRC Submission

067539-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R8110 (G1)

Quality Score

197.009

Status

Validated

Chromosome

Chromosomal Location

52532298-52542585 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 52537709 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Asparagine at position 84 (H84N)

Ref Sequence

ENSEMBL: ENSMUSP00000022767 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000022766] [ENSMUST00000022767] [ENSMUST00000122962] [ENSMUST00000145875] [ENSMUST00000147768] [ENSMUST00000173138] [ENSMUST00000173896] [ENSMUST00000174351] [ENSMUST00000174853]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000022766

SMART Domains

Protein: ENSMUSP00000022766
Gene: ENSMUSG00000016831

Domain	Start	End	E-Value	Type
low complexity region	146	160	N/A	INTRINSIC
low complexity region	207	218	N/A	INTRINSIC
HMG	222	292	1.17e-18	SMART
low complexity region	307	339	N/A	INTRINSIC
low complexity region	435	476	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000022767
AA Change: H84N

PolyPhen 2 Score 0.023 (Sensitivity: 0.95; Specificity: 0.81)

SMART Domains

Protein: ENSMUSP00000022767
Gene: ENSMUSG00000022160
AA Change: H84N

Domain	Start	End	E-Value	Type
low complexity region	53	67	N/A	INTRINSIC
low complexity region	82	93	N/A	INTRINSIC
low complexity region	191	213	N/A	INTRINSIC
Pfam:MT-A70	389	550	9.9e-65	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000122962

Predicted Effect

probably benign
Transcript: ENSMUST00000145875

Predicted Effect

probably benign
Transcript: ENSMUST00000147768
AA Change: H84N

PolyPhen 2 Score 0.375 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000134577
Gene: ENSMUSG00000022160
AA Change: H84N

Domain	Start	End	E-Value	Type
low complexity region	53	67	N/A	INTRINSIC
low complexity region	82	93	N/A	INTRINSIC
low complexity region	191	213	N/A	INTRINSIC
low complexity region	231	242	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000173138
AA Change: H84N

PolyPhen 2 Score 0.548 (Sensitivity: 0.88; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000134018
Gene: ENSMUSG00000022160
AA Change: H84N

Domain	Start	End	E-Value	Type
low complexity region	53	67	N/A	INTRINSIC
low complexity region	82	93	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000173656

SMART Domains

Protein: ENSMUSP00000133759
Gene: ENSMUSG00000022160

Domain	Start	End	E-Value	Type
Pfam:MT-A70	1	60	8.6e-17	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000173896
AA Change: H84N

PolyPhen 2 Score 0.548 (Sensitivity: 0.88; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000133506
Gene: ENSMUSG00000022160
AA Change: H84N

Domain	Start	End	E-Value	Type
low complexity region	53	67	N/A	INTRINSIC
low complexity region	82	93	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000174351
AA Change: H33N

PolyPhen 2 Score 0.338 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000134732
Gene: ENSMUSG00000022160
AA Change: H33N

Domain	Start	End	E-Value	Type
low complexity region	2	16	N/A	INTRINSIC
low complexity region	31	42	N/A	INTRINSIC
low complexity region	140	162	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000174360

SMART Domains

Protein: ENSMUSP00000134578
Gene: ENSMUSG00000022160

Domain	Start	End	E-Value	Type
Pfam:MT-A70	1	34	4.3e-10	PFAM
Pfam:MT-A70	30	74	1.4e-15	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000174853

SMART Domains

Protein: ENSMUSP00000133864
Gene: ENSMUSG00000022160

Domain	Start	End	E-Value	Type
low complexity region	120	142	N/A	INTRINSIC

Coding Region Coverage

1x: 99.9%
3x: 99.7%
10x: 98.6%
20x: 93.1%

Validation Efficiency

99% (73/74)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the 70 kDa subunit of MT-A which is part of N6-adenosine-methyltransferase. This enzyme is involved in the posttranscriptional methylation of internal adenosine residues in eukaryotic mRNAs, forming N6-methyladenosine. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit embryonic lethality between E3.5 and E8.5 with a deficiency in adopting the epiblast egg cylinder. [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
Ankrd45	T	C	1: 160,978,889 (GRCm39)		probably null	Het
Appl1	C	A	14: 26,649,751 (GRCm39)	G592*	probably null	Het
Arfgef2	T	A	2: 166,720,464 (GRCm39)	M1501K	probably benign	Het
Calcrl	C	T	2: 84,169,683 (GRCm39)	A333T	probably damaging	Het
Cd200r3	T	A	16: 44,771,835 (GRCm39)	I33N	probably benign	Het
Ceacam15	A	G	7: 16,407,334 (GRCm39)	L61P	probably benign	Het
Cfap69	T	A	5: 5,632,515 (GRCm39)	H827L	possibly damaging	Het
Csmd3	T	A	15: 47,507,666 (GRCm39)	E2780V	probably damaging	Het
Cyp2u1	G	A	3: 131,087,303 (GRCm39)	T426I	probably damaging	Het
Eefsec	A	C	6: 88,353,312 (GRCm39)	I119S	probably damaging	Het
Fem1b	T	C	9: 62,703,550 (GRCm39)	N570S	probably damaging	Het
Fmo9	A	G	1: 166,491,095 (GRCm39)	M461T	probably benign	Het
Fryl	A	G	5: 73,290,620 (GRCm39)	Y95H	probably benign	Het
Fsip2	T	C	2: 82,789,017 (GRCm39)	I346T	probably benign	Het
Fto	T	C	8: 92,211,818 (GRCm39)	F381S	probably damaging	Het
Gabbr1	G	C	17: 37,359,475 (GRCm39)	S150T	probably benign	Het
Galnt9	G	T	5: 110,763,339 (GRCm39)	W448L	probably damaging	Het
Gcnt2	G	T	13: 41,071,198 (GRCm39)		probably benign	Het
Gm10800	CAAGAAAACTGAAAATCAAAGAAAACTGAAAATCA	CAAGAAAACTGAAAATCA	2: 98,497,361 (GRCm39)		probably null	Het
Gmcl1	G	T	6: 86,698,408 (GRCm39)	A163E	probably damaging	Het
Hectd4	A	G	5: 121,471,012 (GRCm39)	Y2633C	possibly damaging	Het
Hsd11b2	A	G	8: 106,249,266 (GRCm39)	I214V	probably damaging	Het
Hspa12a	T	A	19: 58,809,445 (GRCm39)	E217V	possibly damaging	Het
Itih2	A	G	2: 10,101,948 (GRCm39)	F845L	probably damaging	Het
Kcnn3	T	A	3: 89,568,540 (GRCm39)	L606H	probably damaging	Het
Krt6b	G	A	15: 101,588,577 (GRCm39)	R28C	probably damaging	Het
Lama2	T	A	10: 26,866,866 (GRCm39)	D2876V	probably damaging	Het
Lmbrd2	T	C	15: 9,175,279 (GRCm39)	S397P	probably damaging	Het
Lmf2	C	T	15: 89,236,561 (GRCm39)		probably null	Het
Lrp2	A	G	2: 69,336,797 (GRCm39)	I1325T	probably benign	Het
Ltbp2	A	T	12: 84,850,676 (GRCm39)	C879*	probably null	Het
Map3k1	A	G	13: 111,891,847 (GRCm39)	V1136A	probably damaging	Het
Mia2	A	G	12: 59,155,873 (GRCm39)		probably null	Het
Mlip	G	T	9: 77,146,861 (GRCm39)	T92K	probably damaging	Het
Nalcn	T	A	14: 123,702,113 (GRCm39)	Y466F	probably benign	Het
Nav2	T	A	7: 49,201,698 (GRCm39)	L235*	probably null	Het
Nbn	T	C	4: 15,981,588 (GRCm39)	V560A	probably benign	Het
Ncln	A	T	10: 81,328,987 (GRCm39)	Y144N	possibly damaging	Het
Nfe2l2	A	C	2: 75,509,765 (GRCm39)	D18E	probably benign	Het
Or10aa3	G	A	1: 173,878,091 (GRCm39)	A51T	probably benign	Het
Or12d2	A	G	17: 37,624,604 (GRCm39)	F224L	probably benign	Het
Or1ak2	T	C	2: 36,827,721 (GRCm39)	C197R	possibly damaging	Het
Or5w11	T	C	2: 87,458,951 (GRCm39)	I48T	possibly damaging	Het
Otop3	A	T	11: 115,230,221 (GRCm39)	M33L	probably benign	Het
Pate7	T	C	9: 35,689,329 (GRCm39)	*84W	probably null	Het
Pdzd2	G	A	15: 12,373,592 (GRCm39)	S2181L	probably benign	Het
Phf14	T	C	6: 11,953,422 (GRCm39)	I387T	possibly damaging	Het
Prb1c	C	T	6: 132,338,531 (GRCm39)	G229D	unknown	Het
Prdm9	T	A	17: 15,774,960 (GRCm39)	N318Y	probably damaging	Het
Proca1	A	G	11: 78,095,737 (GRCm39)	D123G	probably damaging	Het
Prune2	G	A	19: 17,098,083 (GRCm39)	G1196S	probably benign	Het
Psd3	T	A	8: 68,573,708 (GRCm39)	S158C	probably damaging	Het
Rps18	A	G	17: 34,174,110 (GRCm39)	V15A	probably benign	Het
Sanbr	G	T	11: 23,526,764 (GRCm39)	T696N	probably benign	Het
Sharpin	C	A	15: 76,231,965 (GRCm39)	R271L	possibly damaging	Het
Smad5	C	A	13: 56,871,701 (GRCm39)	Q99K	probably damaging	Het
Sox5	T	C	6: 144,062,200 (GRCm39)	M151V	possibly damaging	Het
Sphkap	A	T	1: 83,256,492 (GRCm39)	F419Y	possibly damaging	Het
Tbx20	T	A	9: 24,636,821 (GRCm39)	Y422F	probably damaging	Het
Tcirg1	A	C	19: 3,949,099 (GRCm39)	F397V	probably damaging	Het
Tex36	G	A	7: 133,197,012 (GRCm39)	S35F	possibly damaging	Het
Tsen54	G	T	11: 115,705,760 (GRCm39)	A26S	unknown	Het
Usp50	T	A	2: 126,622,250 (GRCm39)		probably null	Het
Vmn2r5	A	T	3: 64,398,709 (GRCm39)	F757I	probably benign	Het
Zbbx	T	C	3: 75,062,749 (GRCm39)	T3A	possibly damaging	Het
Zfp28	T	A	7: 6,392,828 (GRCm39)	M168K	probably benign	Het
Zfp568	G	T	7: 29,722,551 (GRCm39)	G499W	probably damaging	Het
Zfp7	C	G	15: 76,775,131 (GRCm39)	P391R	possibly damaging	Het

Other mutations in Mettl3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00401:Mettl3	APN	14	52,534,424 (GRCm39)	unclassified	probably benign
IGL00508:Mettl3	APN	14	52,532,436 (GRCm39)	unclassified	probably benign
R0417:Mettl3	UTSW	14	52,534,155 (GRCm39)	missense	probably damaging	1.00
R1533:Mettl3	UTSW	14	52,534,385 (GRCm39)	missense	probably benign	0.01
R2113:Mettl3	UTSW	14	52,532,441 (GRCm39)	makesense	probably null
R3785:Mettl3	UTSW	14	52,537,363 (GRCm39)	missense	probably benign	0.15
R3786:Mettl3	UTSW	14	52,537,363 (GRCm39)	missense	probably benign	0.15
R4651:Mettl3	UTSW	14	52,532,549 (GRCm39)	missense	probably damaging	1.00
R4652:Mettl3	UTSW	14	52,532,549 (GRCm39)	missense	probably damaging	1.00
R4938:Mettl3	UTSW	14	52,537,184 (GRCm39)	missense	probably damaging	1.00
R5462:Mettl3	UTSW	14	52,537,336 (GRCm39)	missense	probably damaging	0.96
R6046:Mettl3	UTSW	14	52,536,243 (GRCm39)	missense	possibly damaging	0.91
R6151:Mettl3	UTSW	14	52,532,477 (GRCm39)	missense	probably damaging	1.00
R6169:Mettl3	UTSW	14	52,536,214 (GRCm39)	missense	possibly damaging	0.88
R6225:Mettl3	UTSW	14	52,534,215 (GRCm39)	splice site	probably null
R6282:Mettl3	UTSW	14	52,535,428 (GRCm39)	missense	probably benign	0.01
R8038:Mettl3	UTSW	14	52,537,421 (GRCm39)	missense	possibly damaging	0.80
R9332:Mettl3	UTSW	14	52,534,125 (GRCm39)	missense	probably damaging	1.00
R9757:Mettl3	UTSW	14	52,537,361 (GRCm39)	missense	probably benign	0.00
RF001:Mettl3	UTSW	14	52,537,756 (GRCm39)	missense	probably benign
X0025:Mettl3	UTSW	14	52,535,545 (GRCm39)	splice site	probably null

Predicted Primers

PCR Primer
(F):5'- TCTTGAGTGGCAGGTGCATC -3'
(R):5'- CTAGCGATGCTGGACAGTTG -3'

Sequencing Primer
(F):5'- GCAGGTGCATCTGGCTAAAG -3'
(R):5'- ATGCTGGACAGTTGAACCC -3'

Posted On

2020-06-30