rs4969555

chrX-24056464-A-GchrX-24056464-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001415.4(EIF2S3):c.133+786A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.56 (13506 hom., 18495 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: EIF2S3 NM_001415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.635

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS2: High Homozygotes in GnomAd at 13504 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF2S3	NM_001415.4	c.133+786A>G		intron_variant		ENST00000253039.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2S3	ENST00000253039.9	c.133+786A>G		intron_variant		1	NM_001415.4	P1
EIF2S3	ENST00000423068.1	c.131+786A>G		intron_variant		2
EIF2S3	ENST00000487075.1	n.156+786A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.565 AC: 62676 AN: 110961 Hom.: 13504 Cov.: 23 AF XY: 0.557 AC XY: 18474 AN XY: 33185

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.523

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.566

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.565 AC: 62689 AN: 111013 Hom.: 13506 Cov.: 23 AF XY: 0.556 AC XY: 18495 AN XY: 33247

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.561

Alfa AF: 0.581 Hom.: 6991

Bravo AF: 0.561

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.8
Dann	Benign	0.46

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: rs4969555; hg19: chrX-24074581;