rs121434289
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The ENST00000301305.8(SLC39A4):c.1120G>A(p.Gly374Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000323 in 1,608,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. G374G) has been classified as Likely benign.
Frequency
Consequence
ENST00000301305.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC39A4 | NM_130849.4 | c.1120G>A | p.Gly374Arg | missense_variant | 6/12 | ENST00000301305.8 | NP_570901.3 | |
LOC124902041 | XR_007061145.1 | n.90+246C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC39A4 | ENST00000301305.8 | c.1120G>A | p.Gly374Arg | missense_variant | 6/12 | 1 | NM_130849.4 | ENSP00000301305 | P1 | |
SLC39A4 | ENST00000276833.9 | c.1045G>A | p.Gly349Arg | missense_variant | 5/11 | 2 | ENSP00000276833 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152114Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000210 AC: 5AN: 237714Hom.: 0 AF XY: 0.0000156 AC XY: 2AN XY: 128424
GnomAD4 exome AF: 0.0000336 AC: 49AN: 1456576Hom.: 0 Cov.: 77 AF XY: 0.0000304 AC XY: 22AN XY: 723982
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152114Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74308
ClinVar
Submissions by phenotype
Hereditary acrodermatitis enteropathica Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 2002 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 31, 2023 | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects SLC39A4 function (PMID: 14709598). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 3539). This missense change has been observed in individual(s) with acrodermatitis enteropathica (PMID: 12068297, 26351177). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs121434289, gnomAD 0.005%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 374 of the SLC39A4 protein (p.Gly374Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at