rs80158178

Positions:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 3P and 16B. PM1PP3BP6_Very_StrongBA1

The ENST00000279036.12(PIGT):c.533G>A(p.Arg178Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00404 in 1,614,094 control chromosomes in the GnomAD database, including 330 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R178W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0046 ( 22 hom., cov: 33)

Exomes 𝑓: 0.0040 ( 308 hom. )

Consequence

PIGT
ENST00000279036.12 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 9.35

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PM1

In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 2 uncertain in ENST00000279036.12

PP3

Multiple lines of computational evidence support a deleterious effect 6: Cadd, Dann, max_spliceai, Eigen, FATHMM_MKL, phyloP100way_vertebrate [when AlphaMissense, BayesDel_addAF, MetaRNN, MutationTaster was below the threshold]

BP6

Variant 20-45419334-G-A is Benign according to our data. Variant chr20-45419334-G-A is described in ClinVar as [Benign]. Clinvar id is 474456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-45419334-G-A is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGT	NM_015937.6 linkuse as main transcript	c.533G>A	p.Arg178Gln	missense_variant	4/12	ENST00000279036.12	NP_057021.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGT	ENST00000279036.12 linkuse as main transcript	c.533G>A	p.Arg178Gln	missense_variant	4/12	1	NM_015937.6	ENSP00000279036	P1	Q969N2-1

Frequencies

GnomAD3 genomes

AF:

0.00455

AC:

693

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0315

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0262

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.0170

AC:

4276

AN:

251278

Hom.:

250

AF XY:

0.0126

AC XY:

1716

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.0245

Gnomad SAS exome

AF:

0.000817

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000238

Gnomad OTH exome

AF:

0.0116

GnomAD4 exome

AF:

0.00398

AC:

5819

AN:

1461764

Hom.:

308

Cov.:

AF XY:

0.00345

AC XY:

2507

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.0978

Gnomad4 ASJ exome

AF:

0.000498

Gnomad4 EAS exome

AF:

0.0241

Gnomad4 SAS exome

AF:

0.000870

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000183

Gnomad4 OTH exome

AF:

0.00290

GnomAD4 genome

AF:

0.00457

AC:

696

AN:

152330

Hom.:

Cov.:

AF XY:

0.00466

AC XY:

347

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.0316

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0262

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00461

Hom.:

Bravo

AF:

0.00941

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.0135

AC:

1641

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 25, 2020	- -

Multiple congenital anomalies-hypotonia-seizures syndrome 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.19

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

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.99

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

MetaRNN

Benign

0.0079

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

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.5

M;.;.;M;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.3

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

REVEL

Uncertain

0.38

Sift

Benign

0.045

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

Sift4G

Uncertain

0.043

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

Polyphen

1.0

D;P;.;.;.;.;.;.;.;.

Vest4

0.34

MPC

0.62

ClinPred

0.038

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.54

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.54

Position offset: 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