3-184249764-G-C

Position:

chr3-184249764-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032331.4(EEF1AKMT4):c.70G>C(p.Glu24Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,613,244 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000048 ( 1 hom. )

Consequence

EEF1AKMT4
NM_032331.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.56

Variant links:

Genes affected

EEF1AKMT4 (HGNC:53611): (EEF1A lysine methyltransferase 4) This gene encodes a member of the lysine-specific methyltransferase (KMT) family. The encoded enzyme catalyzes the methylation of lysine-36 of the eukaryotic translation elongation factor 1 alpha. Methylation by this enzyme may affect endoplasmic reticulum-related processes. [provided by RefSeq, Jul 2017]

EEF1AKMT4 links:

EEF1AKMT4-ECE2 (HGNC:53615): (EEF1AKMT4-ECE2 readthrough) This gene represents naturally occurring readthrough transcription between adjacent genes eukaryotic translation elongation factor 1 alpha lysine methyltransferase 4 (GeneID: 110599564) and endothelin converting enzyme 2 (GeneID:9718). The readthrough transcript representing this gene encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jul 2017]

EEF1AKMT4-ECE2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01938054).

BP6

Variant 3-184249764-G-C is Benign according to our data. Variant chr3-184249764-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2552592.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EEF1AKMT4	NM_032331.4 linkuse as main transcript	c.70G>C	p.Glu24Gln	missense_variant	1/3	ENST00000324557.9	NP_115707.2	P0DPD7-4
EEF1AKMT4-ECE2	NM_014693.4 linkuse as main transcript	c.70G>C	p.Glu24Gln	missense_variant	1/19		NP_055508.3	P0DPD6P0DPD8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EEF1AKMT4	ENST00000324557.9 linkuse as main transcript	c.70G>C	p.Glu24Gln	missense_variant	1/3	1	NM_032331.4	ENSP00000314295.5		P0DPD7-4
EEF1AKMT4-ECE2	ENST00000402825.7 linkuse as main transcript	c.70G>C	p.Glu24Gln	missense_variant	1/19	1		ENSP00000384223.3		P0DPD8-1

Frequencies

GnomAD3 genomes

AF:

0.0000985

AC:

AN:

152262

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:

0.00250

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000148

AC:

AN:

250162

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00191

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000479

AC:

AN:

1460864

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

726748

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000907

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.0000984

AC:

AN:

152380

Hom.:

Cov.:

AF XY:

0.0000939

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00251

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000178

ExAC

AF:

0.0000906

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.83

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.32

T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.66

N;N

REVEL

Benign

0.053

Sift

Benign

0.86

T;T

Sift4G

Benign

0.58

T;T

Vest4

0.12

MutPred

0.40

Gain of glycosylation at Y25 (P = 0.0054);Gain of glycosylation at Y25 (P = 0.0054);

MVP

0.60

MPC

0.19

ClinPred

0.027

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.14

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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