rs751861982
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_015937.6(PIGT):c.918dup(p.Val307ArgfsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,613,644 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. D306D) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_015937.6 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGT | NM_015937.6 | c.918dup | p.Val307ArgfsTer13 | frameshift_variant | 8/12 | ENST00000279036.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGT | ENST00000279036.12 | c.918dup | p.Val307ArgfsTer13 | frameshift_variant | 8/12 | 1 | NM_015937.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000461 AC: 7AN: 151776Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251484Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135912
GnomAD4 exome AF: 0.0000718 AC: 105AN: 1461868Hom.: 0 Cov.: 32 AF XY: 0.0000605 AC XY: 44AN XY: 727236
GnomAD4 genome AF: 0.0000461 AC: 7AN: 151776Hom.: 0 Cov.: 32 AF XY: 0.0000540 AC XY: 4AN XY: 74112
ClinVar
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 18, 2024 | The c.918dupC (p.V307Rfs*13) alteration, located in exon 8 (coding exon 8) of the PIGT gene, consists of a duplication of C at position 918, causing a translational frameshift with a predicted alternate stop codon after 13 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the CC allele has an overall frequency of 0.004% (11/282816) total alleles studied. The highest observed frequency was 0.009% (11/129174) of European (non-Finnish) alleles. This variant has been identified in conjunction with other PIGT variants in multiple individuals with features consistent with PIGT-related glycosylphosphatidylinositol deficiency; in at least one instance, the variants were identified in trans (Bayat, 2021; Ambry internal data). Based on the available evidence, this alteration is classified as pathogenic. - |
Multiple congenital anomalies-hypotonia-seizures syndrome 3 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 12, 2019 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 03, 2023 | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34046058, 33620284, 25943031) - |
PIGT-related disorder Other:1
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at