20-45416169-A-G

Position:

chr20-45416169-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_015937.6(PIGT):c.13A>G(p.Met5Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000306 in 1,569,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M5T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

PIGT
NM_015937.6 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

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]

PIGT links:

LOC107985405 (HGNC:):

LOC107985405 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014683872).

BP6

Variant 20-45416169-A-G is Benign according to our data. Variant chr20-45416169-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2652350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGT	NM_015937.6 linkuse as main transcript	c.13A>G	p.Met5Val	missense_variant	1/12	ENST00000279036.12
LOC107985405	XR_001754640.2 linkuse as main transcript	n.819T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGT	ENST00000279036.12 linkuse as main transcript	c.13A>G	p.Met5Val	missense_variant	1/12	1	NM_015937.6	P1	Q969N2-1

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000224

AC:

AN:

178370

Hom.:

AF XY:

0.0000206

AC XY:

AN XY:

97196

show subpopulations

Gnomad AFR exome

AF:

0.000329

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000133

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000254

AC:

AN:

1417520

Hom.:

Cov.:

AF XY:

0.0000242

AC XY:

AN XY:

701804

show subpopulations

Gnomad4 AFR exome

AF:

0.000155

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000246

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000257

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ExAC

AF:

0.0000254

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

PIGT: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.0060

DANN

Benign

0.72

DEOGEN2

Benign

0.0097

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

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.74

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

M_CAP

Benign

0.0078

MetaRNN

Benign

0.015

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

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

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.45

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

REVEL

Benign

0.010

Sift

Benign

0.53

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

Sift4G

Benign

0.27

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

Polyphen

0.0

B;B;.;.;.;.;.;.;.;.;.;.;.;B

Vest4

0.13

MutPred

0.33

Gain of catalytic residue at M5 (P = 0.0344);Gain of catalytic residue at M5 (P = 0.0344);Gain of catalytic residue at M5 (P = 0.0344);Gain of catalytic residue at M5 (P = 0.0344);Gain of catalytic residue at M5 (P = 0.0344);Gain of catalytic residue at M5 (P = 0.0344);Gain of catalytic residue at M5 (P = 0.0344);Gain of catalytic residue at M5 (P = 0.0344);Gain of catalytic residue at M5 (P = 0.0344);Gain of catalytic residue at M5 (P = 0.0344);Gain of catalytic residue at M5 (P = 0.0344);Gain of catalytic residue at M5 (P = 0.0344);Gain of catalytic residue at M5 (P = 0.0344);Gain of catalytic residue at M5 (P = 0.0344);

MVP

0.13

MPC

0.12

ClinPred

0.010

GERP RS

-3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.10

gMVP

0.44

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