18-62045890-C-CT
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_176787.5(PIGN):c.2761dupA(p.Arg921LysfsTer24) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,730 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_176787.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIGN | NM_176787.5 | c.2761dupA | p.Arg921LysfsTer24 | frameshift_variant | Exon 31 of 31 | ENST00000640252.2 | NP_789744.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIGN | ENST00000640252.2 | c.2761dupA | p.Arg921LysfsTer24 | frameshift_variant | Exon 31 of 31 | 1 | NM_176787.5 | ENSP00000492233.1 | ||
PIGN | ENST00000400334.7 | c.2761dupA | p.Arg921LysfsTer24 | frameshift_variant | Exon 30 of 30 | 1 | ENSP00000383188.2 | |||
PIGN | ENST00000638424.1 | n.*729dupA | non_coding_transcript_exon_variant | Exon 29 of 29 | 5 | ENSP00000491963.1 | ||||
PIGN | ENST00000638424.1 | n.*729dupA | 3_prime_UTR_variant | Exon 29 of 29 | 5 | ENSP00000491963.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152168Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461562Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727054
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74332
ClinVar
Submissions by phenotype
Multiple congenital anomalies-hypotonia-seizures syndrome 1 Uncertain:1
This sequence change results in a frameshift in the PIGN gene (p.Arg921Lysfs*24). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 11 amino acid(s) of the PIGN protein and extend the protein by 12 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PIGN-related conditions. ClinVar contains an entry for this variant (Variation ID: 948007). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts the C-terminus of the PIGN protein. Other variant(s) that disrupt this region (p.Lys925*) have been observed in individuals with PIGN-related conditions (PMID: 28273706). This suggests that this may be a clinically significant region of the protein. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at