rs201597085
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_080425.4(GNAS):āc.988A>Gā(p.Ile330Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,613,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. I330I) has been classified as Likely benign.
Frequency
Consequence
NM_080425.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GNAS | NM_016592.5 | c.*42+13367A>G | intron_variant | ENST00000371075.7 | NP_057676.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GNAS | ENST00000676826.2 | c.988A>G | p.Ile330Val | missense_variant | 1/13 | ENSP00000504675.2 | ||||
GNAS | ENST00000371102.8 | c.988A>G | p.Ile330Val | missense_variant | 1/12 | 5 | ENSP00000360143.4 | |||
GNAS | ENST00000371075.7 | c.*42+13367A>G | intron_variant | 1 | NM_016592.5 | ENSP00000360115.3 | ||||
GNAS | ENST00000663479.2 | c.-39+12378A>G | intron_variant | ENSP00000499353.2 | ||||||
GNAS | ENST00000462499.6 | c.-39+12378A>G | intron_variant | 2 | ENSP00000499758.2 | |||||
GNAS | ENST00000467227.6 | c.-39+10179A>G | intron_variant | 3 | ENSP00000499681.2 | |||||
GNAS | ENST00000453292.7 | c.*42+13367A>G | intron_variant | 5 | ENSP00000392000.2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152148Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000770 AC: 19AN: 246786Hom.: 0 AF XY: 0.0000892 AC XY: 12AN XY: 134496
GnomAD4 exome AF: 0.0000356 AC: 52AN: 1460926Hom.: 0 Cov.: 33 AF XY: 0.0000454 AC XY: 33AN XY: 726712
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152266Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74448
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Jul 30, 2021 | - - |
GNAS-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 24, 2024 | The GNAS c.988A>G variant is predicted to result in the amino acid substitution p.Ile330Val. Of note, in the more commonly reported transcript (NM_000516.5) this variant is pre-coding (c.-37474A>G). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.033% of alleles in individuals of East Asian descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at