NM_001404.5:c.619G>A

Variant names:

• chr11-62567432-C-T
• rs1941570365
• NM_001404.5:c.619G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001404.5(EEF1G):​c.619G>A​(p.Val207Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EEF1G NM_001404.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.54

Genes affected

EEF1G (HGNC:3213): (eukaryotic translation elongation factor 1 gamma) This gene encodes a subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome. This subunit contains an N-terminal glutathione transferase domain, which may be involved in regulating the assembly of multisubunit complexes containing this elongation factor and aminoacyl-tRNA synthetases. [provided by RefSeq, Jul 2008]

ENSG00000255508 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEF1G	NM_001404.5	c.619G>A	p.Val207Met	missense_variant	Exon 6 of 10	ENST00000329251.5	NP_001395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEF1G	ENST00000329251.5	c.619G>A	p.Val207Met	missense_variant	Exon 6 of 10	1	NM_001404.5	ENSP00000331901.4
ENSG00000255508	ENST00000496634.2	n.*2669G>A		non_coding_transcript_exon_variant	Exon 13 of 17	2		ENSP00000456163.1
ENSG00000255508	ENST00000496634.2	n.*2669G>A		3_prime_UTR_variant	Exon 13 of 17	2		ENSP00000456163.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.619G>A (p.V207M) alteration is located in exon 6 (coding exon 6) of the EEF1G gene. This alteration results from a G to A substitution at nucleotide position 619, causing the valine (V) at amino acid position 207 to be replaced by a methionine (M). 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	Uncertain	0.37
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.057	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	-0.027	T
MutationAssessor	Pathogenic	3.4	M
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.99	D
Vest4		0.71
MVP		0.68
MPC		1.3
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.54
gMVP		0.54

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

Other links and lift over

dbSNP: rs1941570365; hg19: chr11-62334904;