chr20-45416175-C-T

Position:

chr20-45416175-C-T

Variant summary

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

The NM_015937.6(PIGT):c.19C>T(p.Leu7Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000127 in 1,577,164 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 (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

PIGT
NM_015937.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.05

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]

PIGT links:

LOC107985405 (HGNC:):

LOC107985405 links:

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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=0.25092196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGT	NM_015937.6 linkuse as main transcript	c.19C>T	p.Leu7Phe	missense_variant	1/12	ENST00000279036.12	NP_057021.2
LOC107985405	XR_001754640.2 linkuse as main transcript	n.813G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGT	ENST00000279036.12 linkuse as main transcript	c.19C>T	p.Leu7Phe	missense_variant	1/12	1	NM_015937.6	ENSP00000279036	P1	Q969N2-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.02e-7

AC:

AN:

1424896

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706064

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:

9.13e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Multiple congenital anomalies-hypotonia-seizures syndrome 3

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 11, 2022

This variant has not been reported in the literature in individuals affected with PIGT-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 7 of the PIGT protein (p.Leu7Phe). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.035

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

T;.;.;.;.;.;.;.;.;.;.;.;.;.;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.93

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.036

MetaRNN

Benign

0.17

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;N;N;N;.;.;.;.;.;.;.;.;.;N;.

MutationTaster

Benign

1.0

D;N;N;N;N;N

PrimateAI

Uncertain

0.48

PROVEAN

Benign

0.15

N;N;N;N;.;.;.;.;.;.;.;.;N;.;.

REVEL

Benign

0.15

Sift

Uncertain

0.013

D;D;D;D;.;.;.;.;.;.;.;.;D;.;.

Sift4G

Uncertain

0.046

D;T;D;D;.;.;.;.;.;.;.;.;.;.;.

Polyphen

0.15

B;P;.;.;.;.;.;.;.;.;.;.;.;P;.

Vest4

0.38

MutPred

0.37

Gain of catalytic residue at L7 (P = 0.104);Gain of catalytic residue at L7 (P = 0.104);Gain of catalytic residue at L7 (P = 0.104);Gain of catalytic residue at L7 (P = 0.104);Gain of catalytic residue at L7 (P = 0.104);Gain of catalytic residue at L7 (P = 0.104);Gain of catalytic residue at L7 (P = 0.104);Gain of catalytic residue at L7 (P = 0.104);Gain of catalytic residue at L7 (P = 0.104);Gain of catalytic residue at L7 (P = 0.104);Gain of catalytic residue at L7 (P = 0.104);Gain of catalytic residue at L7 (P = 0.104);Gain of catalytic residue at L7 (P = 0.104);Gain of catalytic residue at L7 (P = 0.104);.;

MVP

0.53

MPC

0.13

ClinPred

0.53

GERP RS

4.7

Varity_R

0.14

gMVP

0.59

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over