8-43158678-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_152419.3(HGSNAT):āc.338T>Cā(p.Leu113Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,459,102 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 Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. L113L) has been classified as Likely benign.
Frequency
Consequence
NM_152419.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HGSNAT | NM_152419.3 | c.338T>C | p.Leu113Pro | missense_variant | 3/18 | ENST00000379644.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HGSNAT | ENST00000379644.9 | c.338T>C | p.Leu113Pro | missense_variant | 3/18 | 2 | NM_152419.3 | P3 | |
HGSNAT | ENST00000520704.1 | c.188T>C | p.Leu63Pro | missense_variant, NMD_transcript_variant | 3/10 | 1 | |||
HGSNAT | ENST00000517319.1 | c.235-245T>C | intron_variant, NMD_transcript_variant | 4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 247590Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134308
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1459102Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2AN XY: 725416
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Mucopolysaccharidosis, MPS-III-C Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | May 23, 2017 | - - |
Mucopolysaccharidosis, MPS-III-C;C4225287:Retinitis pigmentosa 73 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 26, 2021 | This sequence change replaces leucine with proline at codon 113 of the HGSNAT protein (p.Leu113Pro). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs765211666, ExAC 0.004%). This missense change has been observed in individual(s) with mucopolysaccharidosis type IIIC (PMID: 20825431). ClinVar contains an entry for this variant (Variation ID: 552118). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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