3-129061740-A-ATGCC
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000174.5(GP9):c.8_11dupCCTG(p.Trp4CysfsTer70) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_000174.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Bernard Soulier syndrome Pathogenic:1
Variant summary: GP9 c.8_11dupCCTG (p.Trp4CysfsX70) results in a premature termination codon, predicted to cause a truncation of the encoded protein, which is a commonly known mechanism for disease. While the variant is not expected to result in nonsense-mediated decay, it is expected to disrupt the last 173 amino acids of the protein. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 240980 control chromosomes (gnomAD v2.1). To our knowledge, no occurrence of c.8_11dupCCTG in individuals affected with Bernard Soulier Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.