20-58840281-C-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_016592.5(GNAS):c.175C>T(p.Gln59*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_016592.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 36
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Pseudohypoparathyroidism type I A Pathogenic:1
The variant NM_016592.5:c.175C>T (p.Gln59)* introduces a premature stop codon in exon 2 of the gene, likely resulting in a truncated protein or nonsense-mediated decay (NMD). According to ACMG/AMP guidelines, this variant meets the criteria for PVS1 and PM2, supporting its classification as likely pathogenic -
not specified Uncertain:1
Variant summary: GNAS c.-51446C>T (also known as c.175C>T (p.Gln59X) in NM_016592) is located in the untranscribed region upstream of the GNAS gene region. The variant was absent in 244574 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.-51446C>T in individuals affected with GNAS-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 3381217). Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.