rs144641429
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The ENST00000380762.5(HCCS):c.5G>A(p.Gly2Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00207 in 1,202,840 control chromosomes in the GnomAD database, including 4 homozygotes. There are 723 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G2S) has been classified as Benign.
Frequency
Consequence
ENST00000380762.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HCCS | NM_005333.5 | c.5G>A | p.Gly2Asp | missense_variant | 2/7 | ENST00000380762.5 | NP_005324.3 | |
HCCS | NM_001122608.3 | c.5G>A | p.Gly2Asp | missense_variant | 2/7 | NP_001116080.1 | ||
HCCS | NM_001171991.3 | c.5G>A | p.Gly2Asp | missense_variant | 2/7 | NP_001165462.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HCCS | ENST00000380762.5 | c.5G>A | p.Gly2Asp | missense_variant | 2/7 | 1 | NM_005333.5 | ENSP00000370139 | P1 | |
HCCS | ENST00000380763.7 | c.5G>A | p.Gly2Asp | missense_variant | 2/7 | 1 | ENSP00000370140 | P1 | ||
HCCS | ENST00000321143.8 | c.5G>A | p.Gly2Asp | missense_variant | 2/7 | 2 | ENSP00000326579 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00114 AC: 128AN: 112558Hom.: 0 Cov.: 24 AF XY: 0.000864 AC XY: 30AN XY: 34706
GnomAD3 exomes AF: 0.00131 AC: 241AN: 183368Hom.: 0 AF XY: 0.00136 AC XY: 92AN XY: 67800
GnomAD4 exome AF: 0.00217 AC: 2363AN: 1090228Hom.: 4 Cov.: 28 AF XY: 0.00195 AC XY: 693AN XY: 356168
GnomAD4 genome AF: 0.00115 AC: 129AN: 112612Hom.: 0 Cov.: 24 AF XY: 0.000863 AC XY: 30AN XY: 34770
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 14, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 02, 2023 | - - |
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 10, 2015 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 06, 2019 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
HCCS-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 10, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Intellectual disability Benign:1
Benign, no assertion criteria provided | clinical testing | Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille | Jan 01, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at