rs764467903
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_133261.3(GIPC3):c.4G>A(p.Glu2Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,155,790 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_133261.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GIPC3 | NM_133261.3 | c.4G>A | p.Glu2Lys | missense_variant | 1/6 | ENST00000644452.3 | |
GIPC3 | NM_001411144.1 | c.4G>A | p.Glu2Lys | missense_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GIPC3 | ENST00000644452.3 | c.4G>A | p.Glu2Lys | missense_variant | 1/6 | NM_133261.3 | P1 | ||
GIPC3 | ENST00000644946.1 | c.4G>A | p.Glu2Lys | missense_variant | 1/6 |
Frequencies
GnomAD3 genomes ? AF: 0.00105 AC: 160AN: 151720Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00432 AC: 3AN: 694Hom.: 0 AF XY: 0.00476 AC XY: 2AN XY: 420
GnomAD4 exome AF: 0.00108 AC: 1087AN: 1003964Hom.: 1 Cov.: 30 AF XY: 0.00106 AC XY: 503AN XY: 474734
GnomAD4 genome ? AF: 0.00105 AC: 160AN: 151826Hom.: 0 Cov.: 31 AF XY: 0.00124 AC XY: 92AN XY: 74250
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 28, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 25, 2018 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 07, 2017 | The p.Glu2Lys variant in GIPC3 has not been previously reported in individuals w ith hearing loss or in large population studies. Computational prediction tools and conservation analysis suggest that the p.Glu2Lys variant may not impact the protein, though this information is not predictive enough to rule out pathogenic ity. In summary, the clinical significance of the p.Glu2Lys variant is uncertain . - |
GIPC3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 20, 2023 | 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at