X-24057677-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001415.4(EIF2S3):c.306T>C(p.Tyr102=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,210,447 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 46 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., 2 hem., cov: 24)
  • Exomes 𝑓: 0.00011 (0 hom. 44 hem.)
• Consequence: EIF2S3 NM_001415.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.16

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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-24057677-T-C is Benign according to our data. Variant chrX-24057677-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1013362.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.16 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF2S3	NM_001415.4	c.306T>C	p.Tyr102=	synonymous_variant	4/12	ENST00000253039.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2S3	ENST00000253039.9	c.306T>C	p.Tyr102=	synonymous_variant	4/12	1	NM_001415.4	P1
EIF2S3	ENST00000423068.1	c.306T>C	p.Tyr102=	synonymous_variant	4/5	2
EIF2S3	ENST00000487075.1	n.156+1999T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.000116 AC: 13 AN: 112424 Hom.: 0 Cov.: 24 AF XY: 0.0000579 AC XY: 2 AN XY: 34554

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000244

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000437 AC: 8 AN: 183027 Hom.: 0 AF XY: 0.0000444 AC XY: 3 AN XY: 67607

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000366

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000856

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000107 AC: 117 AN: 1098023 Hom.: 0 Cov.: 30 AF XY: 0.000121 AC XY: 44 AN XY: 363395

Gnomad4 AFR exome AF: 0.0000379

Gnomad4 AMR exome AF: 0.0000284

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000128

Gnomad4 OTH exome AF: 0.000152

GnomAD4 genome AF: 0.000116 AC: 13 AN: 112424 Hom.: 0 Cov.: 24 AF XY: 0.0000579 AC XY: 2 AN XY: 34554

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000244

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000285 Hom.: 1

Bravo AF: 0.0000831

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.4
Dann	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs370164270; hg19: chrX-24075794;