3-50300501-C-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_033159.4(HYAL1):āc.1290G>Cā(p.Glu430Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000672 in 1,614,242 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_033159.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HYAL1 | NM_033159.4 | c.1290G>C | p.Glu430Asp | missense_variant | 4/4 | ENST00000395144.7 | NP_149349.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HYAL1 | ENST00000395144.7 | c.1290G>C | p.Glu430Asp | missense_variant | 4/4 | 1 | NM_033159.4 | ENSP00000378576.2 |
Frequencies
GnomAD3 genomes AF: 0.000453 AC: 69AN: 152248Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000529 AC: 133AN: 251436Hom.: 0 AF XY: 0.000522 AC XY: 71AN XY: 135904
GnomAD4 exome AF: 0.000694 AC: 1015AN: 1461876Hom.: 1 Cov.: 31 AF XY: 0.000675 AC XY: 491AN XY: 727240
GnomAD4 genome AF: 0.000453 AC: 69AN: 152366Hom.: 0 Cov.: 33 AF XY: 0.000497 AC XY: 37AN XY: 74506
ClinVar
Submissions by phenotype
Deficiency of hyaluronoglucosaminidase Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 25, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 430 of the HYAL1 protein (p.Glu430Asp). This variant is present in population databases (rs147678727, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with HYAL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 901013). 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 tolerated. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 20, 2024 | The c.1290G>C (p.E430D) alteration is located in exon 6 (coding exon 3) of the HYAL1 gene. This alteration results from a G to C substitution at nucleotide position 1290, causing the glutamic acid (E) at amino acid position 430 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | May 28, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at