Variant 10-124762312-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_212554.4(EEF1AKMT2):c.863C>T(p.Ser288Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,073,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

EEF1AKMT2
NM_212554.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.668

Variant links:

Genes affected

EEF1AKMT2 (HGNC:33787): (EEF1A lysine methyltransferase 2) Enables protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine methylation. Located in cytosol and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

EEF1AKMT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053024918).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EEF1AKMT2	NM_212554.4 linkuse as main transcript	c.863C>T	p.Ser288Leu	missense_variant	6/7	ENST00000368836.7
EEF1AKMT2	NM_001304467.2 linkuse as main transcript	c.629C>T	p.Ser210Leu	missense_variant	6/7
EEF1AKMT2	NM_001304468.2 linkuse as main transcript	c.383-1809C>T		intron_variant
EEF1AKMT2	NM_001416243.1 linkuse as main transcript	c.617-1809C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EEF1AKMT2	ENST00000368836.7 linkuse as main transcript	c.863C>T	p.Ser288Leu	missense_variant	6/7	1	NM_212554.4

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000144

AC:

AN:

69568

Hom.:

AF XY:

0.00

AC XY:

AN XY:

35584

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000152

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000108

AC:

AN:

921768

Hom.:

Cov.:

AF XY:

0.0000115

AC XY:

AN XY:

433928

show subpopulations

Gnomad4 AFR exome

AF:

0.0000540

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000327

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000100

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.0000264

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 01, 2022

The c.863C>T (p.S288L) alteration is located in exon 6 (coding exon 6) of the METTL10 gene. This alteration results from a C to T substitution at nucleotide position 863, causing the serine (S) at amino acid position 288 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.67

CADD

Benign

4.6

DANN

Benign

0.30

DEOGEN2

Benign

0.00089

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.34

M_CAP

Benign

0.0026

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.13

REVEL

Benign

0.0050

Sift

Pathogenic

0.0

Sift4G

Benign

0.30

Polyphen

0.0

Vest4

0.12

MutPred

0.43

Loss of disorder (P = 0.0205);

MVP

0.030

MPC

0.055

ClinPred

0.018

GERP RS

-1.2

Varity_R

0.078

gMVP

0.065

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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