Genetic Variant EEF1AKMT1:p.Arg162Trp (chr13-20731865-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001318939.2(EEF1AKMT1):c.484C>T(p.Arg162Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,590 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

EEF1AKMT1
NM_001318939.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.99

Variant links:

Genes affected

EEF1AKMT1 (HGNC:27351): (EEF1A lysine methyltransferase 1) Enables protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine methylation. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

EEF1AKMT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEF1AKMT1	NM_001318939.2 link	c.484C>T	p.Arg162Trp	missense_variant	Exon 4 of 5	ENST00000382758.6	NP_001305868.1	Q8WVE0A0A024RDN3B2RE94
EEF1AKMT1	NM_174928.3 link	c.484C>T	p.Arg162Trp	missense_variant	Exon 4 of 5		NP_777588.1	Q8WVE0A0A024RDN3
EEF1AKMT1	XM_017020432.2 link	c.484C>T	p.Arg162Trp	missense_variant	Exon 4 of 5		XP_016875921.1	Q8WVE0A0A024RDN3
EEF1AKMT1	NR_134934.2 link	n.461C>T		non_coding_transcript_exon_variant	Exon 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEF1AKMT1	ENST00000382758.6 link	c.484C>T	p.Arg162Trp	missense_variant	Exon 4 of 5	1	NM_001318939.2	ENSP00000372206.1		Q8WVE0
EEF1AKMT1	ENST00000382754.4 link	c.484C>T	p.Arg162Trp	missense_variant	Exon 4 of 5	1		ENSP00000372202.4		Q8WVE0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251340

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461590

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.484C>T (p.R162W) alteration is located in exon 4 (coding exon 3) of the EEF1AKMT1 gene. This alteration results from a C to T substitution at nucleotide position 484, causing the arginine (R) at amino acid position 162 to be replaced by a tryptophan (W). 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

0.13

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;T

Eigen

Benign

-0.042

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.38

LIST_S2

Uncertain

0.96

.;D

M_CAP

Benign

0.071

MetaRNN

Uncertain

0.58

D;D

MetaSVM

Benign

-0.87

PrimateAI

Benign

0.20

PROVEAN

Pathogenic

-5.3

D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

0.96

D;D

Vest4

0.49

MutPred

0.54

Gain of catalytic residue at L167 (P = 0);Gain of catalytic residue at L167 (P = 0);

MVP

0.55

MPC

0.69

ClinPred

0.62

GERP RS

4.1

Varity_R

0.21

gMVP

0.61

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