18-62045906-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_176787.5(PIGN):āc.2746A>Gā(p.Thr916Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,752 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 (ā ā ).
Frequency
Consequence
NM_176787.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIGN | NM_176787.5 | c.2746A>G | p.Thr916Ala | 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.2746A>G | p.Thr916Ala | missense_variant | Exon 31 of 31 | 1 | NM_176787.5 | ENSP00000492233.1 | ||
PIGN | ENST00000400334.7 | c.2746A>G | p.Thr916Ala | missense_variant | Exon 30 of 30 | 1 | ENSP00000383188.2 | |||
PIGN | ENST00000638424.1 | n.*714A>G | non_coding_transcript_exon_variant | Exon 29 of 29 | 5 | ENSP00000491963.1 | ||||
PIGN | ENST00000638424.1 | n.*714A>G | 3_prime_UTR_variant | Exon 29 of 29 | 5 | ENSP00000491963.1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 249032Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135096
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461550Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727052
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74348
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.2746A>G (p.T916A) alteration is located in exon 31 (coding exon 28) of the PIGN gene. This alteration results from a A to G substitution at nucleotide position 2746, causing the threonine (T) at amino acid position 916 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, 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 alanine, which is neutral and non-polar, at codon 916 of the PIGN protein (p.Thr916Ala). This variant is present in population databases (rs754732184, gnomAD 0.03%). 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: 946479). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PIGN protein function with a positive predictive value of 80%. 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