NM_001959.4:c.337G>A

Variant names:

• chr2-206162044-G-A
• rs1687950325
• NM_001959.4:c.337G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001959.4(EEF1B2):​c.337G>A​(p.Glu113Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EEF1B2 NM_001959.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.53
• Publications: 0 publications found

Genes affected

EEF1B2 (HGNC:3208): (eukaryotic translation elongation factor 1 beta 2) This gene encodes a translation elongation factor. The protein is a guanine nucleotide exchange factor involved in the transfer of aminoacylated tRNAs to the ribosome. Alternative splicing results in three transcript variants which differ only in the 5' UTR. [provided by RefSeq, Jul 2008]

SNORA41 (HGNC:32634): (small nucleolar RNA, H/ACA box 41)

SNORD51 (HGNC:10201): (small nucleolar RNA, C/D box 51)

snoZ196 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26748106).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001959.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1B2	NM_001959.4	MANE Select	c.337G>A	p.Glu113Lys	missense	Exon 4 of 6	NP_001950.1	P24534
	EEF1B2	NM_001037663.2		c.337G>A	p.Glu113Lys	missense	Exon 5 of 7	NP_001032752.1	P24534
	EEF1B2	NM_021121.4		c.337G>A	p.Glu113Lys	missense	Exon 5 of 7	NP_066944.1	P24534

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1B2	ENST00000392222.7	TSL:1 MANE Select	c.337G>A	p.Glu113Lys	missense	Exon 4 of 6	ENSP00000376056.2	P24534
	EEF1B2	ENST00000236957.9	TSL:1	c.337G>A	p.Glu113Lys	missense	Exon 5 of 7	ENSP00000236957.5	P24534
	EEF1B2	ENST00000881937.1		c.421G>A	p.Glu141Lys	missense	Exon 6 of 8	ENSP00000551996.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461668 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727132

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111858

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.43	N
PhyloP100		6.5
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.12
Sift	Benign	0.17	T
Sift4G	Benign	0.13	T
Polyphen		0.20	B
Vest4		0.45
MutPred		0.44		Gain of ubiquitination at E113 (P = 0.0077)
MVP		0.62
MPC		0.28
ClinPred		0.96	D
GERP RS		5.1
Varity_R		0.19
gMVP		0.36
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs1687950325; hg19: chr2-207026768;