chr3-50302155-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_033159.4(HYAL1):c.802G>A(p.Glu268Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,614,166 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 (★★).
Frequency
Consequence
NM_033159.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HYAL1 | NM_033159.4 | c.802G>A | p.Glu268Lys | missense_variant | Exon 2 of 4 | ENST00000395144.7 | NP_149349.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251402Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135902
GnomAD4 exome AF: 0.0000479 AC: 70AN: 1461874Hom.: 0 Cov.: 32 AF XY: 0.0000399 AC XY: 29AN XY: 727240
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74470
ClinVar
Submissions by phenotype
Deficiency of hyaluronoglucosaminidase Pathogenic:1Uncertain:1
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 268 of the HYAL1 protein (p.Glu268Lys). This variant is present in population databases (rs104893743, gnomAD 0.02%). This missense change has been observed in individual(s) with mucopolysaccharidosis type IX (PMID: 10339581). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 3530). 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. 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. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at