rs367592728
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001346754.2(PIGW):c.883C>T(p.Arg295Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R295R) has been classified as Likely benign.
Frequency
Consequence
NM_001346754.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGW | NM_001346754.2 | c.883C>T | p.Arg295Trp | missense_variant | 2/2 | ENST00000614443.2 | |
PIGW | NM_001346755.2 | c.883C>T | p.Arg295Trp | missense_variant | 2/2 | ||
PIGW | NM_178517.5 | c.883C>T | p.Arg295Trp | missense_variant | 2/2 | ||
MYO19 | XM_047436823.1 | c.-295-3880G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGW | ENST00000614443.2 | c.883C>T | p.Arg295Trp | missense_variant | 2/2 | 1 | NM_001346754.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251116Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135790
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461710Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19AN XY: 727152
GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74334
ClinVar
Submissions by phenotype
Hyperphosphatasia with intellectual disability syndrome 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 27, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 295 of the PIGW protein (p.Arg295Trp). This variant is present in population databases (rs367592728, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with PIGW-related conditions. ClinVar contains an entry for this variant (Variation ID: 475250). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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