chr18-62045905-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_176787.5(PIGN):c.2747C>T(p.Thr916Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,613,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_176787.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIGN | NM_176787.5 | c.2747C>T | p.Thr916Ile | missense_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.2747C>T | p.Thr916Ile | missense_variant | Exon 31 of 31 | 1 | NM_176787.5 | ENSP00000492233.1 | ||
PIGN | ENST00000400334.7 | c.2747C>T | p.Thr916Ile | missense_variant | Exon 30 of 30 | 1 | ENSP00000383188.2 | |||
PIGN | ENST00000638424.1 | n.*715C>T | non_coding_transcript_exon_variant | Exon 29 of 29 | 5 | ENSP00000491963.1 | ||||
PIGN | ENST00000638424.1 | n.*715C>T | 3_prime_UTR_variant | Exon 29 of 29 | 5 | ENSP00000491963.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249022Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135088
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461516Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727034
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74474
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The p.T916I variant (also known as c.2747C>T), located in coding exon 28 of the PIGN gene, results from a C to T substitution at nucleotide position 2747. The threonine at codon 916 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Multiple congenital anomalies-hypotonia-seizures syndrome 1 Uncertain:1
This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 916 of the PIGN protein (p.Thr916Ile). This variant is present in population databases (rs753641623, gnomAD 0.01%). 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: 1046650). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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