rs985880836
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002641.4(PIGA):c.-75A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000116 in 863,042 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 25)
Exomes 𝑓: 0.0000012 ( 0 hom. 0 hem. )
Consequence
PIGA
NM_002641.4 5_prime_UTR
NM_002641.4 5_prime_UTR
Scores
1
4
5
Clinical Significance
Conservation
PhyloP100: 0.192
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGA | NM_002641.4 | c.-75A>T | 5_prime_UTR_variant | 1/6 | ENST00000333590.6 | ||
PIGA | NM_020473.3 | c.1A>T | p.Met1? | start_lost | 1/5 | ||
PIGA | NR_033835.1 | n.42A>T | non_coding_transcript_exon_variant | 1/6 | |||
PIGA | NR_033836.1 | n.42A>T | non_coding_transcript_exon_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGA | ENST00000333590.6 | c.-75A>T | 5_prime_UTR_variant | 1/6 | 1 | NM_002641.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 25
GnomAD3 genomes
?
Cov.:
25
GnomAD4 exome AF: 0.00000116 AC: 1AN: 863042Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 265800
GnomAD4 exome
AF:
AC:
1
AN:
863042
Hom.:
Cov.:
28
AF XY:
AC XY:
0
AN XY:
265800
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 25
GnomAD4 genome
?
Cov.:
25
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 31, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); Initiation codon variant in an alternate transcript; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
Sift4G
Pathogenic
D
Vest4
MutPred
Loss of disorder (P = 0.2078);
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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
Publications
No publications associated with this variant yet.