rs763418298

Variant names:

• chrX-24055651-A-C
• rs763418298
• NM_001415.4:c.106A>C

Your query was ambiguous. Multiple possible variants found:

• chrX-24055651-A-C
• chrX-24055651-A-G

Variant summary

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

The NM_001415.4(EIF2S3):​c.106A>C​(p.Ile36Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I36V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: EIF2S3 NM_001415.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.28

Genes affected

EIF2S3 (HGNC:3267): (eukaryotic translation initiation factor 2 subunit gamma) The protein encoded by this gene is the largest subunit of a heterotrimeric GTP-binding protein involved in the recruitment of methionyl-tRNA(i) to the 40 S ribosomal subunit. [provided by RefSeq, Jan 2010]

ACMG classification

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
EIF2S3	NM_001415.4	c.106A>C	p.Ile36Leu	missense_variant	Exon 2 of 12	ENST00000253039.9	NP_001406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF2S3	ENST00000253039.9	c.106A>C	p.Ile36Leu	missense_variant	Exon 2 of 12	1	NM_001415.4	ENSP00000253039.4
EIF2S3	ENST00000423068.1	c.103A>C	p.Ile35Leu	missense_variant	Exon 2 of 5	2		ENSP00000391383.1
EIF2S3	ENST00000487075.1	n.129A>C		non_coding_transcript_exon_variant	Exon 2 of 3	5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Uncertain	0.057	D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.028	D
Sift4G	Benign	0.094	T
Polyphen		0.18	B
Vest4		0.61
MutPred		0.77		Gain of loop (P = 0.1069);
MVP		0.85
MPC		0.83
ClinPred		0.96	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.75
gMVP		0.84

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: rs763418298; hg19: chrX-24073768;