Variant rs17650204 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_015935.5(METTL13):c.966A>G(p.Lys322Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 1,613,564 control chromosomes in the GnomAD database, including 7,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.072 ( 556 hom., cov: 32)

Exomes 𝑓: 0.092 ( 6816 hom. )

Consequence

METTL13
NM_015935.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.26

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:

METTL13 (HGNC:):

METTL13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 1-171785931-A-G is Benign according to our data. Variant chr1-171785931-A-G is described in ClinVar as [Benign]. Clinvar id is 3055433.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=3.26 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL13	NM_015935.5 linkuse as main transcript	c.966A>G	p.Lys322Lys	synonymous_variant	3/8	ENST00000361735.4	NP_057019.3	Q8N6R0-5C4B4C6
METTL13	NM_014955.3 linkuse as main transcript	c.708A>G	p.Lys236Lys	synonymous_variant	3/8		NP_055770.1	Q8N6R0-3
METTL13	NM_001007239.2 linkuse as main transcript	c.498A>G	p.Lys166Lys	synonymous_variant	3/8		NP_001007240.1	Q8N6R0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
METTL13	ENST00000361735.4 linkuse as main transcript	c.966A>G	p.Lys322Lys	synonymous_variant	3/8	1	NM_015935.5	ENSP00000354920.3	Q8N6R0-5
METTL13	ENST00000367737.9 linkuse as main transcript	c.498A>G	p.Lys166Lys	synonymous_variant	3/8	1		ENSP00000356711.5	Q8N6R0-1
METTL13	ENST00000362019.7 linkuse as main transcript	c.708A>G	p.Lys236Lys	synonymous_variant	3/8	2		ENSP00000355393.3	Q8N6R0-3
METTL13	ENST00000485629.1 linkuse as main transcript	n.610A>G		non_coding_transcript_exon_variant	4/4	5

Frequencies

GnomAD3 genomes

AF:

0.0717

AC:

10903

AN:

152068

Hom.:

556

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0164

Gnomad AMI

AF:

0.100

Gnomad AMR

AF:

0.0554

Gnomad ASJ

AF:

0.0966

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0272

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.0665

GnomAD3 exomes

AF:

0.0750

AC:

18791

AN:

250640

Hom.:

952

AF XY:

0.0761

AC XY:

10311

AN XY:

135516

show subpopulations

Gnomad AFR exome

AF:

0.0139

Gnomad AMR exome

AF:

0.0371

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0298

Gnomad FIN exome

AF:

0.118

Gnomad NFE exome

AF:

0.109

Gnomad OTH exome

AF:

0.0824

GnomAD4 exome

AF:

0.0915

AC:

133722

AN:

1461378

Hom.:

6816

Cov.:

AF XY:

0.0906

AC XY:

65879

AN XY:

726948

show subpopulations

Gnomad4 AFR exome

AF:

0.0130

Gnomad4 AMR exome

AF:

0.0387

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0310

Gnomad4 FIN exome

AF:

0.118

Gnomad4 NFE exome

AF:

0.103

Gnomad4 OTH exome

AF:

0.0845

GnomAD4 genome

AF:

0.0716

AC:

10904

AN:

152186

Hom.:

556

Cov.:

AF XY:

0.0708

AC XY:

5267

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0164

Gnomad4 AMR

AF:

0.0554

Gnomad4 ASJ

AF:

0.0966

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0272

Gnomad4 FIN

AF:

0.117

Gnomad4 NFE

AF:

0.109

Gnomad4 OTH

AF:

0.0658

Alfa

AF:

0.0985

Hom.:

1965

Bravo

AF:

0.0635

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.107

EpiControl

AF:

0.102

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

METTL13-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 11, 2019

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

-0.47

CADD

Benign

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over