Mutagenetix > Incidental Mutation

Incidental Mutation 'R4651:Mettl3'

386321

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

041911-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4651 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

52532298-52542585 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 52532549 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Phenylalanine at position 545 (I545F)

Ref Sequence

ENSEMBL: ENSMUSP00000022767 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000022766] [ENSMUST00000022767] [ENSMUST00000122962] [ENSMUST00000147768] [ENSMUST00000174351] [ENSMUST00000153539] [ENSMUST00000173138] [ENSMUST00000173896] [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 damaging
Transcript: ENSMUST00000022767
AA Change: I545F

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000022767
Gene: ENSMUSG00000022160
AA Change: I545F

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

noncoding transcript
Transcript: ENSMUST00000127797

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000130550

Predicted Effect

probably benign
Transcript: ENSMUST00000147768

SMART Domains

Protein: ENSMUSP00000134577
Gene: ENSMUSG00000022160

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

noncoding transcript
Transcript: ENSMUST00000152493

Predicted Effect

unknown
Transcript: ENSMUST00000173656
AA Change: D52V

SMART Domains

Protein: ENSMUSP00000133759
Gene: ENSMUSG00000022160
AA Change: D52V

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000173546

Predicted Effect

unknown
Transcript: ENSMUST00000174360
AA Change: I68F

SMART Domains

Protein: ENSMUSP00000134578
Gene: ENSMUSG00000022160
AA Change: I68F

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: ENSMUST00000174351

SMART Domains

Protein: ENSMUSP00000134732
Gene: ENSMUSG00000022160

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: ENSMUST00000153539

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000156611

Predicted Effect

probably benign
Transcript: ENSMUST00000173138

SMART Domains

Protein: ENSMUSP00000134018
Gene: ENSMUSG00000022160

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: ENSMUST00000173896

SMART Domains

Protein: ENSMUSP00000133506
Gene: ENSMUSG00000022160

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: ENSMUST00000174853

SMART Domains

Protein: ENSMUSP00000133864
Gene: ENSMUSG00000022160

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

Meta Mutation Damage Score

0.3724

Coding Region Coverage

1x: 99.3%
3x: 98.6%
10x: 97.3%
20x: 95.3%

Validation Efficiency

97% (98/101)

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: 91 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2700049A03Rik	G	T	12: 71,211,320 (GRCm39)	E685*	probably null	Het
2700049A03Rik	A	T	12: 71,211,321 (GRCm39)	E685V	possibly damaging	Het
4933409G03Rik	G	A	2: 68,436,559 (GRCm39)	E168K	unknown	Het
Ahnak2	T	G	12: 112,741,271 (GRCm39)	S128R	possibly damaging	Het
Ankrd26	T	C	6: 118,492,787 (GRCm39)	D1319G	probably benign	Het
Ankrd35	T	C	3: 96,591,343 (GRCm39)	V543A	probably benign	Het
Ano10	A	T	9: 122,090,181 (GRCm39)	Y377*	probably null	Het
Arsi	G	A	18: 61,049,723 (GRCm39)	G202E	probably benign	Het
Atp10b	G	A	11: 43,085,472 (GRCm39)	G284S	probably damaging	Het
Atp5f1c	A	G	2: 10,068,287 (GRCm39)	F180S	probably damaging	Het
Btnl4	A	G	17: 34,691,602 (GRCm39)	S296P	probably benign	Het
Cast	A	G	13: 74,894,133 (GRCm39)	S171P	probably benign	Het
Catsperb	G	A	12: 101,507,771 (GRCm39)	A513T	probably benign	Het
Ccnf	C	A	17: 24,450,760 (GRCm39)	R406L	probably damaging	Het
Ceacam12	A	G	7: 17,801,359 (GRCm39)	T113A	probably damaging	Het
Cipc	T	C	12: 87,008,864 (GRCm39)	V241A	probably benign	Het
Col12a1	A	T	9: 79,520,228 (GRCm39)	D2815E	probably damaging	Het
Cpox	G	T	16: 58,491,050 (GRCm39)	R87L	possibly damaging	Het
Cttnbp2	A	G	6: 18,434,037 (GRCm39)	I607T	possibly damaging	Het
Cux1	A	T	5: 136,596,083 (GRCm39)	N4K	probably damaging	Het
Cyp3a25	T	C	5: 145,931,701 (GRCm39)	T136A	probably benign	Het
Dhx58	T	A	11: 100,592,185 (GRCm39)	N288Y	probably damaging	Het
Dnah10	T	C	5: 124,806,207 (GRCm39)	Y127H	probably benign	Het
Dnd1	G	A	18: 36,898,114 (GRCm39)		probably benign	Het
Ehmt2	C	A	17: 35,132,790 (GRCm39)	N1171K	probably damaging	Het
Fanci	T	A	7: 79,085,004 (GRCm39)	M838K	possibly damaging	Het
Flot1	T	C	17: 36,143,436 (GRCm39)		probably benign	Het
Gad2	A	T	2: 22,558,374 (GRCm39)	D364V	probably damaging	Het
Gm10375	C	A	14: 43,844,326 (GRCm39)		probably null	Het
Gm9996	T	A	10: 29,019,754 (GRCm39)		probably benign	Het
Gnat3	T	A	5: 18,220,568 (GRCm39)	L247H	probably damaging	Het
Ip6k3	C	T	17: 27,364,265 (GRCm39)	C261Y	probably damaging	Het
Irgc	C	A	7: 24,132,238 (GRCm39)	R193L	probably damaging	Het
Kalrn	G	T	16: 33,996,761 (GRCm39)	P1477Q	probably damaging	Het
Kyat1	G	T	2: 30,084,076 (GRCm39)	H15N	probably benign	Het
Lamc1	T	G	1: 153,104,523 (GRCm39)	S59R	probably damaging	Het
Llgl1	A	G	11: 60,599,477 (GRCm39)	D486G	possibly damaging	Het
Lrrc9	T	C	12: 72,524,160 (GRCm39)	W790R	probably damaging	Het
Lsm2	T	A	17: 35,204,571 (GRCm39)		probably benign	Het
Med8	A	T	4: 118,268,089 (GRCm39)	E5V	probably damaging	Het
Mefv	A	G	16: 3,535,682 (GRCm39)	L82P	probably damaging	Het
Mettl25b	T	C	3: 87,834,979 (GRCm39)	H107R	probably benign	Het
Naa20	CTCTAGA	C	2: 145,753,752 (GRCm39)		probably benign	Het
Ncapg2	T	A	12: 116,389,407 (GRCm39)	N342K	probably damaging	Het
Ndufaf6	T	A	4: 11,062,070 (GRCm39)	Y187F	probably damaging	Het
Nomo1	T	A	7: 45,717,866 (GRCm39)	I799N	probably damaging	Het
Obscn	G	A	11: 58,929,703 (GRCm39)	R5824C	probably damaging	Het
Or4f6	G	T	2: 111,838,595 (GRCm39)	S312Y	probably damaging	Het
Or6c214	T	C	10: 129,591,287 (GRCm39)	I11V	probably benign	Het
Or6n2	A	G	1: 173,897,394 (GRCm39)	I177V	possibly damaging	Het
Or7g30	T	A	9: 19,352,591 (GRCm39)	C127*	probably null	Het
Pgm3	T	A	9: 86,440,523 (GRCm39)	R389S	probably benign	Het
Pkd2l2	A	T	18: 34,542,889 (GRCm39)	R20*	probably null	Het
Pkhd1	T	A	1: 20,451,747 (GRCm39)	I2183F	probably damaging	Het
Ppp4r3a	T	A	12: 101,049,170 (GRCm39)		probably benign	Het
Prpf38b	G	A	3: 108,811,408 (GRCm39)		probably benign	Het
Prpf4b	A	T	13: 35,083,954 (GRCm39)	M908L	probably benign	Het
Prps2	T	C	X: 166,135,288 (GRCm39)	D183G	probably damaging	Het
Prrc2c	A	T	1: 162,550,843 (GRCm39)	H40Q	probably damaging	Het
Ptprk	T	C	10: 28,139,686 (GRCm39)	I137T	probably damaging	Het
Sdr42e1	T	C	8: 118,390,360 (GRCm39)	T94A	probably benign	Het
Setd2	A	G	9: 110,423,200 (GRCm39)	D2085G	possibly damaging	Het
Sgce	T	C	6: 4,689,560 (GRCm39)		probably benign	Het
Shisa3	A	G	5: 67,765,992 (GRCm39)	D81G	probably damaging	Het
Sipa1l1	T	A	12: 82,469,245 (GRCm39)	L1248*	probably null	Het
Skint7	T	G	4: 111,839,309 (GRCm39)	M201R	probably damaging	Het
Slc5a3	T	A	16: 91,874,090 (GRCm39)	V49E	probably benign	Het
Slc9c1	A	T	16: 45,367,756 (GRCm39)	*163L	probably null	Het
Smyd3	A	G	1: 178,871,306 (GRCm39)	Y358H	probably benign	Het
Srp68	A	T	11: 116,164,840 (GRCm39)	S31R	probably benign	Het
Stag1	T	A	9: 100,678,769 (GRCm39)	M230K	probably damaging	Het
Strc	A	T	2: 121,204,829 (GRCm39)	D985E	possibly damaging	Het
Syne2	A	G	12: 76,036,013 (GRCm39)	T3767A	probably damaging	Het
Sytl2	C	A	7: 90,024,633 (GRCm39)	P207Q	probably damaging	Het
Tbc1d2b	A	G	9: 90,089,940 (GRCm39)	F863S	probably damaging	Het
Tek	T	C	4: 94,669,121 (GRCm39)	S41P	probably damaging	Het
Top1	T	C	2: 160,554,637 (GRCm39)	Y463H	probably damaging	Het
Trim24	T	G	6: 37,934,774 (GRCm39)		probably null	Het
Trim38	A	T	13: 23,966,952 (GRCm39)	D133V	probably damaging	Het
Ttn	A	G	2: 76,576,979 (GRCm39)	V24638A	possibly damaging	Het
Ttn	A	G	2: 76,701,213 (GRCm39)		probably benign	Het
Tyro3	G	C	2: 119,647,349 (GRCm39)	G826A	probably benign	Het
Ube2b	A	G	11: 51,886,199 (GRCm39)		probably null	Het
Ubxn4	T	A	1: 128,202,587 (GRCm39)	W410R	probably benign	Het
Unc45a	T	C	7: 79,982,777 (GRCm39)	K383E	possibly damaging	Het
Usp7	A	C	16: 8,516,278 (GRCm39)		probably benign	Het
Vmn1r193	C	T	13: 22,403,695 (GRCm39)	G99D	probably damaging	Het
Vrk2	T	C	11: 26,439,803 (GRCm39)	D256G	probably damaging	Het
Wdr81	A	G	11: 75,342,066 (GRCm39)	V1067A	probably damaging	Het
Wiz	C	T	17: 32,576,655 (GRCm39)	R624Q	probably damaging	Het
Zcwpw2	A	G	9: 117,843,119 (GRCm39)		noncoding transcript	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
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
R8110:Mettl3	UTSW	14	52,537,709 (GRCm39)	missense	probably benign	0.02
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'- AACAGTCCTCTTAAGGTGTGGC -3'
(R):5'- GACACTGCCATATTATTTGCTCTGATC -3'

Sequencing Primer
(F):5'- TTAGAGATGATGCCGTCC -3'
(R):5'- CCTGGTCTACAAAGTGAGTTCCAG -3'

Genotyping

Genotyping is performed by amplifying the region containing the mutation using PCR, followed by sequencing of the amplified region to detect the mutation.

PCR Primers

R46510082_PCR_F: 5’- AACAGTCCTCTTAAGGTGTGGC-3’

R46510082_PCR_R: 5’- GACACTGCCATATTATTTGCTCTGATC-3’

Sequencing Primers

R46510082_SEQ_F: 5’- TTAGAGATGATGCCGTCC-3’ 

R46510082_SEQ_R: 5’- CCTGGTCTACAAAGTGAGTTCCAG-3’ 

PCR program

1) 94°C 2:00

2) 94°C 0:30

3) 55°C 0:30

4) 72°C 1:00

5) repeat steps (2-4) 40X

6) 72°C 10:00

7) 4°C hold

The following sequence of 592 nucleotides is amplified (NCBI RefSeq: NC_000080, chromosome 14:52294915-52295506):

aacagtcctc ttaaggtgtg gcctgtagcc catggctctg aacgcttagc tttgtaagga

agtgcgtcta taaattctta ggtttagaga tgatgccgtc cggatacctt tgcttaaacc

tggcaaccac atctgggtct agtaggtgta tcccatccag ttggtttcca agagtaatcc

taaaacaagg gggaaagaag aggcaaacca aaaatcctgt aagggcttaa tacttaaaat

gttctacttt ctggtgatac ctatctcagg ctgtcctgga actaactctc catgtagacc

aggctaacct tgaactcaga gatctacttg cctctgcctc ccaagtgctg aggctaaagg

tgtgctctac tatgcccagt ccacgtcaat ttttttggtt tggtttggtt tggtttttga

gacagggttt ctttgtatag ccccggctga cctggaactc actttgtaga ccaggctggc

ttcagaaatc cacctgccta tgcctcctga gtgctgggat taaaggcatg cgccaccacg

cccggcctac atcaactttt aaaaagatca gagcaaataa tatggcagtg tc

Primer binding sites are underlined and the sequencing primer is highlighted; the mutated nucleotide is shown in red text (Chr. (+) = T>A).

Posted On

2016-05-11