NM_153747.2:c.61C>T
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_153747.2(PIGC):c.61C>T(p.Arg21*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000725 in 1,613,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_153747.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000302 AC: 46AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251434Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135898
GnomAD4 exome AF: 0.0000486 AC: 71AN: 1461658Hom.: 0 Cov.: 34 AF XY: 0.0000413 AC XY: 30AN XY: 727148
GnomAD4 genome AF: 0.000302 AC: 46AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15AN XY: 74472
ClinVar
Submissions by phenotype
Glycosylphosphatidylinositol biosynthesis defect 16 Pathogenic:4
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This variant is interpreted as Likely Pathogenic, for Glycosylphosphatidylinositol biosynthesis defect 16, autosomal recessive. The following ACMG Tag(s) were applied: PVS1-Moderate => PVS1 downgraded in strength to Moderate. PS3-Moderate => PS3 downgraded in strength to Moderate (https://www.ncbi.nlm.nih.gov/pubmed/27694521). PM2 => Recessive disease and allele present at low frequency in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. -
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The c.61C>T;p.(Arg21)* variant creates a premature translational stop signal in the PIGC gene. It is expected to result in an absent or disrupted protein product -PVS1_moderate. Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 27694521) - PS3_supporting. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 471153; PMID: 27694521) - PS4. The variant is present at low allele frequencies population databases (rs115209243 – gnomAD 0.0007425%; ABraOM 0.000854 frequency - http://abraom.ib.usp.br) - PM2_supporting. The p.(Arg21*) was detected in trans with a pathogenic variant (PMID: 27694521) - PM3. The variant co-segregated with disease in multiple affected family members (PMID: 27694521) - PP1. In summary, the currently available evidence indicates that the variant is pathogenic -
not provided Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at