rs587777027
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_015937.6(PIGT):āc.547A>Cā(p.Thr183Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,800 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 Likely pathogenic (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.0000027 ( 0 hom. )
Consequence
PIGT
NM_015937.6 missense
NM_015937.6 missense
Scores
11
7
1
Clinical Significance
Conservation
PhyloP100: 8.71
Genes affected
PIGT (HGNC:14938): (phosphatidylinositol glycan anchor biosynthesis class T) This gene encodes a protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This protein is an essential component of the multisubunit enzyme, GPI transamidase. GPI transamidase mediates GPI anchoring in the endoplasmic reticulum, by catalyzing the transfer of fully assembled GPI units to proteins. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PM1
?
In a helix (size 8) in uniprot entity PIGT_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_015937.6
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.971
PP5
?
Variant 20-45419348-A-C is Pathogenic according to our data. Variant chr20-45419348-A-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 64649.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-45419348-A-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGT | NM_015937.6 | c.547A>C | p.Thr183Pro | missense_variant | 4/12 | ENST00000279036.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGT | ENST00000279036.12 | c.547A>C | p.Thr183Pro | missense_variant | 4/12 | 1 | NM_015937.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461800Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727198
GnomAD4 exome
AF:
AC:
4
AN:
1461800
Hom.:
Cov.:
31
AF XY:
AC XY:
3
AN XY:
727198
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
Bravo
AF:
EpiCase
AF:
EpiControl
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Multiple congenital anomalies-hypotonia-seizures syndrome 3 Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Centre for Inherited Metabolic Diseases, Karolinska University Hospital | Mar 20, 2024 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.;.;.;.;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.;.;H;.;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;.;.;.;.;.;.
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D;.;.;.;.;.;.
Sift4G
Pathogenic
D;D;D;D;.;.;.;.;.;.
Polyphen
D;D;.;.;.;.;.;.;.;.
Vest4
MutPred
Loss of phosphorylation at T183 (P = 0.0398);.;.;Loss of phosphorylation at T183 (P = 0.0398);Loss of phosphorylation at T183 (P = 0.0398);Loss of phosphorylation at T183 (P = 0.0398);.;.;.;.;
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