rs200024253
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001346754.2(PIGW):āc.499A>Gā(p.Met167Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,244 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M167I) has been classified as Uncertain significance.
Frequency
Consequence
NM_001346754.2 missense
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGW | NM_001346754.2 | c.499A>G | p.Met167Val | missense_variant | 2/2 | ENST00000614443.2 | |
PIGW | NM_001346755.2 | c.499A>G | p.Met167Val | missense_variant | 2/2 | ||
PIGW | NM_178517.5 | c.499A>G | p.Met167Val | missense_variant | 2/2 | ||
MYO19 | XM_047436823.1 | c.-295-3496T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGW | ENST00000614443.2 | c.499A>G | p.Met167Val | missense_variant | 2/2 | 1 | NM_001346754.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152126Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251454Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135904
GnomAD4 exome Cov.: 32
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74418
ClinVar
Submissions by phenotype
Hyperphosphatasia with intellectual disability syndrome 5 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2014 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 22, 2020 | Variant summary: PIGW c.499A>G (p.Met167Val) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251454 control chromosomes (gnomAD). c.499A>G has been reported in the literature in at least one individual affected with glycosylphosphatidylinositol anchor deficiency (Chiyonobu_2014). At least one publication reports experimental evidence evaluating an impact on protein function and showed that this variant affects the restoration of GPI-APs expression (Chiyonobu_2014). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at