chr1-109548838-G-C
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_006496.4(GNAI3):c.118G>C(p.Gly40Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 15/25 in silico tools predict a damaging outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_006496.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GNAI3 | NM_006496.4 | c.118G>C | p.Gly40Arg | missense_variant, splice_region_variant | 1/9 | ENST00000369851.7 | NP_006487.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GNAI3 | ENST00000369851.7 | c.118G>C | p.Gly40Arg | missense_variant, splice_region_variant | 1/9 | 1 | NM_006496.4 | ENSP00000358867 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 26
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Auriculocondylar syndrome 1 Pathogenic:2
Pathogenic, criteria provided, single submitter | research | University of Washington Center for Mendelian Genomics, University of Washington | Sep 17, 2012 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | May 04, 2012 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 18, 2023 | In silico analyses support that this missense variant has a deleterious effect on protein structure/function and may impact gene splicing; in the absence of RNA/functional studies, the actual effect of this sequence change is unknown; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 22560091) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at