chr8-43140502-CG-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_152419.3(HGSNAT):c.10del(p.Ala4ArgfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000224 in 892,532 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. G3G) has been classified as Likely benign.
Frequency
Consequence
NM_152419.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HGSNAT | NM_152419.3 | c.10del | p.Ala4ArgfsTer15 | frameshift_variant | 1/18 | ENST00000379644.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HGSNAT | ENST00000379644.9 | c.10del | p.Ala4ArgfsTer15 | frameshift_variant | 1/18 | 2 | NM_152419.3 | P3 | |
HGSNAT | ENST00000517319.1 | c.10del | p.Ala4ArgfsTer15 | frameshift_variant, NMD_transcript_variant | 1/5 | 4 | |||
HGSNAT | ENST00000520704.1 | upstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000224 AC: 2AN: 892532Hom.: 0 Cov.: 29 AF XY: 0.00000240 AC XY: 1AN XY: 417534
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Mucopolysaccharidosis, MPS-III-C;C4225287:Retinitis pigmentosa 73 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 17, 2022 | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with HGSNAT-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala4Argfs*15) in the HGSNAT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HGSNAT are known to be pathogenic (PMID: 17033958, 19479962). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.