4-500405-C-A

Position:

chr4-500405-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001127178.3(PIGG):c.164C>A(p.Ser55Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00206 in 1,612,718 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 35 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 29 hom. )

Consequence

PIGG
NM_001127178.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 6.38

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:

PIGG (HGNC:):

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=0.006947577).

BP6

Variant 4-500405-C-A is Benign according to our data. Variant chr4-500405-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 445328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1742/152214) while in subpopulation AFR AF= 0.039 (1619/41514). AF 95% confidence interval is 0.0374. There are 35 homozygotes in gnomad4. There are 813 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 35 BG,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGG	NM_001127178.3 linkuse as main transcript	c.164C>A	p.Ser55Tyr	missense_variant	2/13	ENST00000453061.7	NP_001120650.1	Q5H8A4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGG	ENST00000453061.7 linkuse as main transcript	c.164C>A	p.Ser55Tyr	missense_variant	2/13	1	NM_001127178.3	ENSP00000415203.2		Q5H8A4-1

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1740

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0391

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00616

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00303

AC:

761

AN:

251394

Hom.:

AF XY:

0.00216

AC XY:

293

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.0420

Gnomad AMR exome

AF:

0.00194

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:

0.0000264

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00109

AC:

1588

AN:

1460504

Hom.:

Cov.:

AF XY:

0.000903

AC XY:

656

AN XY:

726636

show subpopulations

Gnomad4 AFR exome

AF:

0.0386

Gnomad4 AMR exome

AF:

0.00228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.00257

GnomAD4 genome

AF:

0.0114

AC:

1742

AN:

152214

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

813

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0390

Gnomad4 AMR

AF:

0.00615

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00125

Hom.:

Bravo

AF:

0.0142

ESP6500AA

AF:

0.0409

AC:

180

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00383

AC:

465

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 08, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 23, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Intellectual disability, autosomal recessive 53

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.47

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

.;T;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

D;D;D

MetaRNN

Benign

0.0069

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.4

M;M;M

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.10

Sift

Uncertain

0.0090

D;D;D

Sift4G

Benign

0.084

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.46

MVP

0.39

MPC

0.77

ClinPred

0.010

GERP RS

4.4

Varity_R

0.29

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