chr20-45416216-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015937.6(PIGT):ā€‹c.60G>Cā€‹(p.Trp20Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,595,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000049 ( 0 hom. )

Consequence

PIGT
NM_015937.6 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.692
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12765107).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PIGTNM_015937.6 linkuse as main transcriptc.60G>C p.Trp20Cys missense_variant 1/12 ENST00000279036.12 NP_057021.2
LOC107985405XR_001754640.2 linkuse as main transcriptn.772C>G non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PIGTENST00000279036.12 linkuse as main transcriptc.60G>C p.Trp20Cys missense_variant 1/121 NM_015937.6 ENSP00000279036 P1Q969N2-1

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152260
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000485
AC:
7
AN:
1443098
Hom.:
0
Cov.:
31
AF XY:
0.00000698
AC XY:
5
AN XY:
716402
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000634
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152260
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.0000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 31, 2023The c.60G>C (p.W20C) alteration is located in exon 1 (coding exon 1) of the PIGT gene. This alteration results from a G to C substitution at nucleotide position 60, causing the tryptophan (W) at amino acid position 20 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
17
DANN
Benign
0.75
DEOGEN2
Benign
0.0079
T;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Eigen
Benign
-0.58
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.59
D
LIST_S2
Uncertain
0.97
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.13
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.69
N;N;N;N;.;.;.;.;.;.;.;.;.;N;.
MutationTaster
Benign
0.74
D;N;N;N;N;N
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-0.37
N;D;N;N;.;.;.;.;.;.;.;.;.;.;.
REVEL
Benign
0.11
Sift
Benign
0.20
T;D;T;T;.;.;.;.;.;.;.;.;.;.;.
Sift4G
Benign
0.18
T;T;T;T;.;.;.;.;.;.;.;.;.;.;.
Polyphen
0.23
B;B;.;.;.;.;.;.;.;.;.;.;.;B;.
Vest4
0.35
MutPred
0.52
Gain of disorder (P = 0.056);Gain of disorder (P = 0.056);Gain of disorder (P = 0.056);Gain of disorder (P = 0.056);Gain of disorder (P = 0.056);Gain of disorder (P = 0.056);Gain of disorder (P = 0.056);Gain of disorder (P = 0.056);Gain of disorder (P = 0.056);Gain of disorder (P = 0.056);Gain of disorder (P = 0.056);Gain of disorder (P = 0.056);Gain of disorder (P = 0.056);Gain of disorder (P = 0.056);.;
MVP
0.33
MPC
0.19
ClinPred
0.096
T
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.10
gMVP
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1432217189; hg19: chr20-44044856; API