1-1436947-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_022834.5(VWA1):c.94C>T(p.Arg32*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 1,607,494 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_022834.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152216Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000409 AC: 10AN: 244670Hom.: 0 AF XY: 0.0000451 AC XY: 6AN XY: 133032
GnomAD4 exome AF: 0.0000165 AC: 24AN: 1455278Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 723194
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
Neuromuscular disease Pathogenic:1
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Neuronopathy, distal hereditary motor, autosomal recessive 7 Pathogenic:1
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VWA1-related disorder Pathogenic:1
The VWA1 c.94C>T variant is predicted to result in premature protein termination (p.Arg32*). This variant has been reported in the compound heterozygous state in an individual with neuromyopathy (Table 1, Deschauer et al. 2021. PubMed ID: 33459760). This variant is reported in 0.019% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-1372327-C-T). Nonsense variants in VWA1 are expected to be pathogenic. This variant is interpreted as likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at