1-172442093-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_153747.2(PIGC):c.530T>C(p.Leu177Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,888 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L177L) has been classified as Likely benign.
Frequency
Consequence
NM_153747.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGC | NM_153747.2 | c.530T>C | p.Leu177Pro | missense_variant | 2/2 | ENST00000344529.5 | |
C1orf105 | NM_139240.4 | c.22-2980A>G | intron_variant | ENST00000367727.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGC | ENST00000344529.5 | c.530T>C | p.Leu177Pro | missense_variant | 2/2 | 1 | NM_153747.2 | P1 | |
C1orf105 | ENST00000367727.9 | c.22-2980A>G | intron_variant | 1 | NM_139240.4 | P1 | |||
PIGC | ENST00000484368.1 | n.96+1895T>C | intron_variant, non_coding_transcript_variant | 1 | |||||
PIGC | ENST00000367728.1 | c.530T>C | p.Leu177Pro | missense_variant | 1/1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251426Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135886
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461888Hom.: 0 Cov.: 39 AF XY: 0.00000963 AC XY: 7AN XY: 727244
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 07, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 177 of the PIGC protein (p.Leu177Pro). This variant is present in population databases (rs372409223, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with PIGC-related conditions. ClinVar contains an entry for this variant (Variation ID: 1924079). 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 PIGC 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