7-80135278-G-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_002069.6(GNAI1):c.118G>T(p.Gly40Cys) 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. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G40R) has been classified as Pathogenic.
Frequency
Consequence
NM_002069.6 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNAI1 | NM_002069.6 | c.118G>T | p.Gly40Cys | missense_variant, splice_region_variant | 1/8 | ENST00000649796.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNAI1 | ENST00000649796.2 | c.118G>T | p.Gly40Cys | missense_variant, splice_region_variant | 1/8 | NM_002069.6 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1322588Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0AN XY: 652314
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | May 02, 2022 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.