rs1318217031
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_152419.3(HGSNAT):c.1042G>A(p.Val348Met) 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. V348V) has been classified as Likely benign.
Frequency
Consequence
NM_152419.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HGSNAT | NM_152419.3 | c.1042G>A | p.Val348Met | missense_variant | 11/18 | ENST00000379644.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HGSNAT | ENST00000379644.9 | c.1042G>A | p.Val348Met | missense_variant | 11/18 | 2 | NM_152419.3 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Mucopolysaccharidosis, MPS-III-C Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Undiagnosed Diseases Network, NIH | Aug 09, 2017 | Two heterozygous variants of unknown significance, c.1042G>A (p.V348M) and c.1267G>T (p.G423W) were detected in the HGSNAT gene in this individual. Whole exome sequencing and Sanger confirmation showed that the father is heterozygous for the p.V348M change, and the mother is heterozygous for the p.G423W change. Our data indicate that the two changes in HGSNAT are in trans (compound heterozygous) configuration. - |
Mucopolysaccharidosis, MPS-III-C;C4225287:Retinitis pigmentosa 73 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2023 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 348 of the HGSNAT protein (p.Val348Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with HGSNAT-related conditions. ClinVar contains an entry for this variant (Variation ID: 522867). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HGSNAT protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at