rs4969555

Variant names:

• chrX-24056464-A-G
• rs4969555
• NM_001415.4:c.133+786A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-24056464-A-G
• chrX-24056464-A-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

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
• Publications: 0 publications found

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]

EIF2S3 Gene-Disease associations (from GenCC):

• MEHMO syndrome

  Inheritance: XL, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, ClinGen, Genomics England PanelApp
• diabetes mellitus

  Inheritance: XL Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF2S3	NM_001415.4	c.133+786A>G		intron_variant	Intron 2 of 11	ENST00000253039.9	NP_001406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF2S3	ENST00000253039.9	c.133+786A>G		intron_variant	Intron 2 of 11	1	NM_001415.4	ENSP00000253039.4
EIF2S3	ENST00000423068.1	c.130+786A>G		intron_variant	Intron 2 of 4	2		ENSP00000391383.1
EIF2S3	ENST00000487075.1	n.156+786A>G		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.565 AC: 62676 AN: 110961 Hom.: 13504 Cov.: 23

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

African (AFR) AF: 0.361 AC: 11046 AN: 30597

American (AMR) AF: 0.627 AC: 6498 AN: 10361

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 1653 AN: 2648

East Asian (EAS) AF: 0.360 AC: 1268 AN: 3520

South Asian (SAS) AF: 0.223 AC: 609 AN: 2736

European-Finnish (FIN) AF: 0.689 AC: 4004 AN: 5808

Middle Eastern (MID) AF: 0.514 AC: 111 AN: 216

European-Non Finnish (NFE) AF: 0.682 AC: 36110 AN: 52933

Other (OTH) AF: 0.561 AC: 852 AN: 1520

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
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

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: rs4969555; hg19: chrX-24074581;