chr4-102267901-A-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate
The NM_001135146.2(SLC39A8):c.1019T>A(p.Ile340Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I340M) has been classified as Uncertain significance.
Frequency
Consequence
NM_001135146.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC39A8 | NM_001135146.2 | c.1019T>A | p.Ile340Asn | missense_variant | 7/9 | ENST00000356736.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC39A8 | ENST00000356736.5 | c.1019T>A | p.Ile340Asn | missense_variant | 7/9 | 1 | NM_001135146.2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
SLC39A8-CDG Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 03, 2015 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 08, 2023 | Published functional studies suggest a damaging effect (Choi et al., 2018; Fujishiro et al., 2022); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26637978, 26637979, 29453449, 28749473, 35636252) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at