rs527917900
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The ENST00000374695.8(HSPG2):c.10028C>T(p.Ala3343Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,612,456 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★★). Synonymous variant affecting the same amino acid position (i.e. A3343A) has been classified as Likely benign.
Frequency
Consequence
ENST00000374695.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HSPG2 | NM_005529.7 | c.10028C>T | p.Ala3343Val | missense_variant | 74/97 | ENST00000374695.8 | NP_005520.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HSPG2 | ENST00000374695.8 | c.10028C>T | p.Ala3343Val | missense_variant | 74/97 | 1 | NM_005529.7 | ENSP00000363827 | P1 | |
HSPG2 | ENST00000374676.4 | c.62C>T | p.Ala21Val | missense_variant | 1/2 | 3 | ENSP00000363808 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000363 AC: 9AN: 248036Hom.: 0 AF XY: 0.0000519 AC XY: 7AN XY: 134792
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1460140Hom.: 0 Cov.: 33 AF XY: 0.0000289 AC XY: 21AN XY: 726196
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152316Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74476
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 24, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 12, 2023 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 447534). This variant has not been reported in the literature in individuals affected with HSPG2-related conditions. This variant is present in population databases (rs527917900, gnomAD 0.008%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3343 of the HSPG2 protein (p.Ala3343Val). - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 13, 2017 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 16, 2023 | The c.10028C>T (p.A3343V) alteration is located in exon 73 (coding exon 73) of the HSPG2 gene. This alteration results from a C to T substitution at nucleotide position 10028, causing the alanine (A) at amino acid position 3343 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at