1-171794409-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_015935.5(METTL13):c.1707C>T(p.Tyr569Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,613,952 control chromosomes in the GnomAD database, including 30,214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.15 ( 2140 hom., cov: 33)

Exomes 𝑓: 0.19 ( 28074 hom. )

Consequence

METTL13
NM_015935.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.32

Publications

22 publications found

Variant links:

Genes affected

METTL13 (HGNC:24248): (methyltransferase 13, eEF1A N-terminus and K55) Predicted to enable methyltransferase activity. Involved in negative regulation of cell cycle G1/S phase transition and negative regulation of transcription by RNA polymerase II. Predicted to be located in mitochondrion and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

METTL13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 1-171794409-C-T is Benign according to our data. Variant chr1-171794409-C-T is described in CliVar as Benign. Clinvar id is 3058980.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-171794409-C-T is described in CliVar as Benign. Clinvar id is 3058980.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-171794409-C-T is described in CliVar as Benign. Clinvar id is 3058980.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-171794409-C-T is described in CliVar as Benign. Clinvar id is 3058980.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-171794409-C-T is described in CliVar as Benign. Clinvar id is 3058980.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-171794409-C-T is described in CliVar as Benign. Clinvar id is 3058980.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-171794409-C-T is described in CliVar as Benign. Clinvar id is 3058980.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-171794409-C-T is described in CliVar as Benign. Clinvar id is 3058980.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-171794409-C-T is described in CliVar as Benign. Clinvar id is 3058980.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-171794409-C-T is described in CliVar as Benign. Clinvar id is 3058980.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.32 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL13	NM_015935.5 link	c.1707C>T	p.Tyr569Tyr	synonymous_variant	Exon 7 of 8	ENST00000361735.4	NP_057019.3	Q8N6R0-5C4B4C6
METTL13	NM_014955.3 link	c.1449C>T	p.Tyr483Tyr	synonymous_variant	Exon 7 of 8		NP_055770.1	Q8N6R0-3
METTL13	NM_001007239.2 link	c.1239C>T	p.Tyr413Tyr	synonymous_variant	Exon 7 of 8		NP_001007240.1	Q8N6R0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METTL13	ENST00000361735.4 link	c.1707C>T	p.Tyr569Tyr	synonymous_variant	Exon 7 of 8	1	NM_015935.5	ENSP00000354920.3		Q8N6R0-5

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23077

AN:

152110

Hom.:

2140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0494

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.155

GnomAD2 exomes

AF:

0.167

AC:

41936

AN:

251312

AF XY:

0.168

show subpopulations

Gnomad AFR exome

AF:

0.0442

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.174

Gnomad EAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.207

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.191

AC:

279499

AN:

1461724

Hom.:

28074

Cov.:

AF XY:

0.189

AC XY:

137597

AN XY:

727168

show subpopulations

African (AFR)

AF:

0.0440

AC:

1473

AN:

33476

American (AMR)

AF:

0.145

AC:

6468

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

4548

AN:

26130

East Asian (EAS)

AF:

0.0901

AC:

3575

AN:

39694

South Asian (SAS)

AF:

0.111

AC:

9551

AN:

86254

European-Finnish (FIN)

AF:

0.206

AC:

10978

AN:

53398

Middle Eastern (MID)

AF:

0.139

AC:

799

AN:

5768

European-Non Finnish (NFE)

AF:

0.208

AC:

231286

AN:

1111904

Other (OTH)

AF:

0.179

AC:

10821

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

12212

24425

36637

48850

61062

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7774

15548

23322

31096

38870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.152

AC:

23064

AN:

152228

Hom.:

2140

Cov.:

AF XY:

0.150

AC XY:

11194

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0492

AC:

2045

AN:

41550

American (AMR)

AF:

0.145

AC:

2222

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

592

AN:

3472

East Asian (EAS)

AF:

0.110

AC:

570

AN:

5184

South Asian (SAS)

AF:

0.103

AC:

498

AN:

4824

European-Finnish (FIN)

AF:

0.210

AC:

2225

AN:

10596

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.211

AC:

14345

AN:

67990

Other (OTH)

AF:

0.153

AC:

322

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1004

2008

3012

4016

5020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

254

508

762

1016

1270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.187

Hom.:

6397

Bravo

AF:

0.143

Asia WGS

AF:

0.105

AC:

364

AN:

3478

EpiCase

AF:

0.207

EpiControl

AF:

0.201

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

METTL13-related disorder

Benign:1

Nov 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

7.3

(source)

DANN

Benign

0.81

PhyloP100

-2.3

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over