chr2-88557424-C-CTA
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_004836.7(EIF2AK3):c.*311_*312insTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00706 in 356,034 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0061 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0078 ( 5 hom. )
Consequence
EIF2AK3
NM_004836.7 3_prime_UTR
NM_004836.7 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.564
Genes affected
EIF2AK3 (HGNC:3255): (eukaryotic translation initiation factor 2 alpha kinase 3) The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2, leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. This protein is thought to modulate mitochondrial function. It is a type I membrane protein located in the endoplasmic reticulum (ER), where it is induced by ER stress caused by malfolded proteins. Mutations in this gene are associated with Wolcott-Rallison syndrome. [provided by RefSeq, Sep 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00611 (926/151544) while in subpopulation NFE AF= 0.00819 (555/67790). AF 95% confidence interval is 0.00762. There are 1 homozygotes in gnomad4. There are 486 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAdExome4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EIF2AK3 | NM_004836.7 | c.*311_*312insTA | 3_prime_UTR_variant | 17/17 | ENST00000303236.9 | ||
LOC101928371 | NR_110236.1 | n.651-17078_651-17077dup | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EIF2AK3 | ENST00000303236.9 | c.*311_*312insTA | 3_prime_UTR_variant | 17/17 | 1 | NM_004836.7 | P1 | ||
ENST00000413234.1 | n.651-17078_651-17077dup | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.00612 AC: 926AN: 151426Hom.: 1 Cov.: 32
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GnomAD4 exome AF: 0.00776 AC: 1587AN: 204490Hom.: 5 Cov.: 0 AF XY: 0.00724 AC XY: 785AN XY: 108466
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GnomAD4 genome AF: 0.00611 AC: 926AN: 151544Hom.: 1 Cov.: 32 AF XY: 0.00656 AC XY: 486AN XY: 74048
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Wolcott-Rallison dysplasia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at