rs587777400
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_002641.4(PIGA):c.278C>T(p.Pro93Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 24)
Consequence
PIGA
NM_002641.4 missense
NM_002641.4 missense
Scores
13
2
1
Clinical Significance
Conservation
PhyloP100: 9.48
Genes affected
PIGA (HGNC:8957): (phosphatidylinositol glycan anchor biosynthesis class A) This gene encodes a protein required for synthesis of N-acetylglucosaminyl phosphatidylinositol (GlcNAc-PI), the first intermediate in the biosynthetic pathway of GPI anchor. The GPI anchor is a glycolipid found on many blood cells and which serves to anchor proteins to the cell surface. Paroxysmal nocturnal hemoglobinuria, an acquired hematologic disorder, has been shown to result from mutations in this gene. Alternate splice variants have been characterized. A related pseudogene is located on chromosome 12. [provided by RefSeq, Jun 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PM1
?
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 2 benign, 9 uncertain in NM_002641.4
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.953
PP5
?
Variant X-15331653-G-A is Pathogenic according to our data. Variant chrX-15331653-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 132819.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-15331653-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGA | NM_002641.4 | c.278C>T | p.Pro93Leu | missense_variant | 2/6 | ENST00000333590.6 | |
PIGA | NM_020473.3 | c.13+3848C>T | intron_variant | ||||
PIGA | NR_033835.1 | n.394C>T | non_coding_transcript_exon_variant | 2/6 | |||
PIGA | NR_033836.1 | n.173+221C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGA | ENST00000333590.6 | c.278C>T | p.Pro93Leu | missense_variant | 2/6 | 1 | NM_002641.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 genomes
?
Cov.:
24
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 24
GnomAD4 genome
?
Cov.:
24
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Multiple congenital anomalies-hypotonia-seizures syndrome 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Pathogenic
D;D;.;.
FATHMM_MKL
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;.;.
REVEL
Pathogenic
Sift
Pathogenic
D;.;.;.
Sift4G
Pathogenic
D;D;D;.
Polyphen
D;D;D;.
Vest4
MutPred
Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at