rs200199765
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_176787.5(PIGN):c.181G>T(p.Glu61Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,408 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 (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_176787.5 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGN | NM_176787.5 | c.181G>T | p.Glu61Ter | stop_gained | 4/31 | ENST00000640252.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGN | ENST00000640252.2 | c.181G>T | p.Glu61Ter | stop_gained | 4/31 | 1 | NM_176787.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152146Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 248942Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 135038
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461262Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 726872
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152146Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74328
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Oct 04, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Oct 24, 2016 | The E61X variant in the PIGN gene has not been reported previously as a pathogenic variant nor as abenign variant, to our knowledge. This variant is predicted to cause loss of normal protein functioneither through protein truncation or nonsense-mediated mRNA decay. The E61X variant was notobserved at a significant frequency in approximately 6100 individuals of European and AfricanAmerican ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret E61X as a pathogenic variant. - |
Multiple congenital anomalies-hypotonia-seizures syndrome 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 15, 2023 | This sequence change creates a premature translational stop signal (p.Glu61*) 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). This variant is present in population databases (rs200199765, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with PIGN-related conditions (PMID: 29096607). ClinVar contains an entry for this variant (Variation ID: 373038). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at