chr3-184249713-G-A

Position:

• chr3-184249713-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032331.4(EEF1AKMT4):​c.19G>A​(p.Gly7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EEF1AKMT4 NM_032331.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.606

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-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]

ACMG classification

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=0.03965375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EEF1AKMT4	NM_032331.4	c.19G>A	p.Gly7Ser	missense_variant	1/3	ENST00000324557.9	NP_115707.2
EEF1AKMT4-ECE2	NM_014693.4	c.19G>A	p.Gly7Ser	missense_variant	1/19		NP_055508.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EEF1AKMT4	ENST00000324557.9	c.19G>A	p.Gly7Ser	missense_variant	1/3	1	NM_032331.4	ENSP00000314295.5
EEF1AKMT4-ECE2	ENST00000402825.7	c.19G>A	p.Gly7Ser	missense_variant	1/19	1		ENSP00000384223.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

The c.19G>A (p.G7S) alteration is located in exon 1 (coding exon 1) of the ECE2 gene. This alteration results from a G to A substitution at nucleotide position 19, causing the glycine (G) at amino acid position 7 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	0.081
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.65
DANN	Benign	0.79
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.41	T;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.040	T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.52	N;N
REVEL	Benign	0.063
Sift	Benign	1.0	T;T
Sift4G	Benign	0.72	T;D
Vest4		0.039
MutPred		0.20		Loss of glycosylation at P11 (P = 0.0076);Loss of glycosylation at P11 (P = 0.0076);
MVP		0.44
MPC		0.19
ClinPred		0.040	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.022
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-183967501; COSMIC: COSV61081040; COSMIC: COSV61081040;