rs34916638

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001127178.3(PIGG):c.2191G>A(p.Val731Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00606 in 1,613,802 control chromosomes in the GnomAD database, including 472 homozygotes. 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 Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 241 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 231 hom. )

Consequence

PIGG
NM_001127178.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.51

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

intellectual disability, autosomal recessive 53
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

PIGG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030880868).

BP6

Variant 4-527160-G-A is Benign according to our data. Variant chr4-527160-G-A is described in ClinVar as Benign. ClinVar VariationId is 476333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGG	NM_001127178.3 link	c.2191G>A	p.Val731Ile	missense_variant	Exon 10 of 13	ENST00000453061.7	NP_001120650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGG	ENST00000453061.7 link	c.2191G>A	p.Val731Ile	missense_variant	Exon 10 of 13	1	NM_001127178.3	ENSP00000415203.2

Frequencies

GnomAD3 genomes

AF:

0.0324

AC:

4931

AN:

152164

Hom.:

240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0145

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.0258

GnomAD2 exomes

AF:

0.00850

AC:

2122

AN:

249546

AF XY:

0.00609

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.00635

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000303

Gnomad OTH exome

AF:

0.00459

GnomAD4 exome

AF:

0.00331

AC:

4840

AN:

1461520

Hom.:

231

Cov.:

AF XY:

0.00286

AC XY:

2077

AN XY:

727056

show subpopulations

African (AFR)

AF:

0.114

AC:

3799

AN:

33440

American (AMR)

AF:

0.00716

AC:

320

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26118

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.000244

AC:

AN:

86198

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00298

AC:

AN:

5710

European-Non Finnish (NFE)

AF:

0.000211

AC:

235

AN:

1111906

Other (OTH)

AF:

0.00737

AC:

445

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

216

433

649

866

1082

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0325

AC:

4942

AN:

152282

Hom.:

241

Cov.:

AF XY:

0.0318

AC XY:

2365

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.111

AC:

4623

AN:

41546

American (AMR)

AF:

0.0146

AC:

223

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000622

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000470

AC:

AN:

68020

Other (OTH)

AF:

0.0256

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

217

433

650

866

1083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0181

Hom.:

Bravo

AF:

0.0390

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.111

AC:

488

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.0105

AC:

1278

Asia WGS

AF:

0.00866

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 28, 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

0.077

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0

.;T;T;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.098

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.86

D;D;D;D

MetaRNN

Benign

0.0031

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

.;L;.;.

PhyloP100

1.5

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.48

N;N;N;N

REVEL

Benign

0.051

Sift

Benign

0.082

T;T;T;T

Sift4G

Benign

0.65

T;T;T;T

Vest4

0.051

ClinPred

0.010

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.034

gMVP

0.29

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over