rs13115344

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001127178.3(PIGG):c.1373G>A(p.Arg458His) variant causes a missense change. The variant allele was found at a frequency of 0.126 in 1,613,798 control chromosomes in the GnomAD database, including 15,332 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.18 ( 3146 hom., cov: 33)

Exomes 𝑓: 0.12 ( 12186 hom. )

Consequence

PIGG
NM_001127178.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.00

Variant links:

Genes affected

PIGG (HGNC:25985): (phosphatidylinositol glycan anchor biosynthesis class G (EMM blood group)) This gene encodes an enzyme involved in glycosylphosphatidylinositol-anchor biosynthesis. The encoded protein, which is localized to the endoplasmic reticulum, is involved in transferring ethanoloamine phosphate to mannose 2 of glycosylphosphatidylinositol species H7 to form species H8. Allelic variants of this gene have been associated with intellectual disability, hypotonia, and early-onset seizures. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

PIGG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043239594).

BP6

Variant 4-521700-G-A is Benign according to our data. Variant chr4-521700-G-A is described in ClinVar as [Benign]. Clinvar id is 1170159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGG	NM_001127178.3 link	c.1373G>A	p.Arg458His	missense_variant	Exon 8 of 13	ENST00000453061.7	NP_001120650.1	Q5H8A4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGG	ENST00000453061.7 link	c.1373G>A	p.Arg458His	missense_variant	Exon 8 of 13	1	NM_001127178.3	ENSP00000415203.2		Q5H8A4-1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27114

AN:

151994

Hom.:

3121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.169

GnomAD3 exomes

AF:

0.133

AC:

33318

AN:

251376

Hom.:

2738

AF XY:

0.130

AC XY:

17713

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.343

Gnomad AMR exome

AF:

0.0637

Gnomad ASJ exome

AF:

0.160

Gnomad EAS exome

AF:

0.198

Gnomad SAS exome

AF:

0.128

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.113

Gnomad OTH exome

AF:

0.124

GnomAD4 exome

AF:

0.121

AC:

176807

AN:

1461686

Hom.:

12186

Cov.:

AF XY:

0.121

AC XY:

87926

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.338

Gnomad4 AMR exome

AF:

0.0717

Gnomad4 ASJ exome

AF:

0.161

Gnomad4 EAS exome

AF:

0.232

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.126

Gnomad4 NFE exome

AF:

0.110

Gnomad4 OTH exome

AF:

0.131

GnomAD4 genome

AF:

0.179

AC:

27191

AN:

152112

Hom.:

3146

Cov.:

AF XY:

0.177

AC XY:

13168

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.332

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.160

Gnomad4 EAS

AF:

0.199

Gnomad4 SAS

AF:

0.131

Gnomad4 FIN

AF:

0.128

Gnomad4 NFE

AF:

0.113

Gnomad4 OTH

AF:

0.169

Alfa

AF:

0.125

Hom.:

3093

Bravo

AF:

0.185

TwinsUK

AF:

0.107

AC:

398

ALSPAC

AF:

0.110

AC:

425

ESP6500AA

AF:

0.333

AC:

1467

ESP6500EA

AF:

0.115

AC:

987

ExAC

AF:

0.138

AC:

16701

Asia WGS

AF:

0.175

AC:

607

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 08, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Intellectual disability, autosomal recessive 53

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.0

DANN

Benign

0.76

DEOGEN2

Benign

0.011

.;T;T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.42

T;T;T;T;T

MetaRNN

Benign

0.0043

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.55

.;N;.;.;.

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.43

N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.55

T;T;T;T;T

Sift4G

Benign

0.54

T;T;T;T;T

Polyphen

0.0

B;B;.;B;B

Vest4

0.069

MPC

0.21

ClinPred

0.0041

GERP RS

1.2

Varity_R

0.012

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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