Variant 10-124789137-T-C 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.197A>G(p.Asn66Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,612,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

EEF1AKMT2
NM_212554.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.19

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=0.024576813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EEF1AKMT2	NM_212554.4 linkuse as main transcript	c.197A>G	p.Asn66Ser	missense_variant	3/7	ENST00000368836.7
EEF1AKMT2	NM_001416243.1 linkuse as main transcript	c.197A>G	p.Asn66Ser	missense_variant	3/6
EEF1AKMT2	NM_001304467.2 linkuse as main transcript	c.-42A>G		5_prime_UTR_variant	3/7
EEF1AKMT2	NM_001304468.2 linkuse as main transcript	c.-42A>G		5_prime_UTR_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
EEF1AKMT2	ENST00000368836.7 linkuse as main transcript	c.197A>G	p.Asn66Ser	missense_variant	3/7	1	NM_212554.4
EEF1AKMT2	ENST00000464099.5 linkuse as main transcript	c.197A>G	p.Asn66Ser	missense_variant, NMD_transcript_variant	3/6	1
EEF1AKMT2	ENST00000466270.5 linkuse as main transcript	c.197A>G	p.Asn66Ser	missense_variant, NMD_transcript_variant	3/7	1
EEF1AKMT2	ENST00000652548.2 linkuse as main transcript	c.197A>G	p.Asn66Ser	missense_variant	3/6			P1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

250870

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135596

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000959

AC:

AN:

1460604

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726658

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000102

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Jan 08, 2024

The c.197A>G (p.N66S) alteration is located in exon 3 (coding exon 3) of the METTL10 gene. This alteration results from a A to G substitution at nucleotide position 197, causing the asparagine (N) at amino acid position 66 to be replaced by a serine (S). 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

0.083

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.58

CADD

Benign

2.0

DANN

Benign

0.64

DEOGEN2

Benign

0.0030

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.73

M_CAP

Benign

0.0038

MetaRNN

Benign

0.025

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.75

REVEL

Benign

0.064

Sift

Benign

0.68

Sift4G

Benign

0.60

Polyphen

0.022

Vest4

0.045

MVP

0.22

MPC

0.052

ClinPred

0.28

GERP RS

-3.8

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.14

gMVP

0.17

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