17-80215120-C-G
Variant summary
Our verdict is Pathogenic. Variant got 22 ACMG points: 22P and 0B. PS1_Very_StrongPM2PP3_StrongPP5_Very_Strong
The NM_000199.5(SGSH):c.268G>C(p.Gly90Arg) 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. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin ClinVar. Synonymous variant affecting the same amino acid position (i.e. G90G) has been classified as Likely benign.
Frequency
Consequence
NM_000199.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 22 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGSH | NM_000199.5 | c.268G>C | p.Gly90Arg | missense_variant | 3/8 | ENST00000326317.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGSH | ENST00000326317.11 | c.268G>C | p.Gly90Arg | missense_variant | 3/8 | 1 | NM_000199.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Mucopolysaccharidosis, MPS-III-A Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2020 | This sequence change replaces glycine with arginine at codon 90 of the SGSH protein (p.Gly90Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. 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. A different variant (c.268G>A) giving rise to the same protein effect observed here (p.Gly90Arg) has been determined to be pathogenic (PMID: 21204211, 21455105, 24875751). This suggests that this variant is also likely to be causative of disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SGSH-related conditions. This variant is not present in population databases (ExAC no frequency). - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 03, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.