18-62147082-T-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_176787.5(PIGN):c.694A>T(p.Lys232Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000137 in 1,603,972 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 Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. K232K) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_176787.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGN | NM_176787.5 | c.694A>T | p.Lys232Ter | stop_gained | 9/31 | ENST00000640252.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGN | ENST00000640252.2 | c.694A>T | p.Lys232Ter | stop_gained | 9/31 | 1 | NM_176787.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000820 AC: 2AN: 244014Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 132336
GnomAD4 exome AF: 0.0000138 AC: 20AN: 1451768Hom.: 0 Cov.: 38 AF XY: 0.0000138 AC XY: 10AN XY: 722360
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
Multiple congenital anomalies-hypotonia-seizures syndrome 1 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 22, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 264641). This premature translational stop signal has been observed in individual(s) with PIGN-related conditions (PMID: 27038415, 28327575, 32220244). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Lys232*) in the PIGN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PIGN are known to be pathogenic (PMID: 24253414, 27038415). - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 29, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at