rs17069506

Variant summary

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

The NM_176787.5(PIGN):c.484A>G(p.Lys162Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0438 in 1,587,798 control chromosomes in the GnomAD database, including 2,017 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 251 hom., cov: 32)

Exomes 𝑓: 0.043 ( 1766 hom. )

Consequence

PIGN
NM_176787.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0490

Variant links:

Genes affected

PIGN (HGNC:8967): (phosphatidylinositol glycan anchor biosynthesis class N) 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 expressed in the endoplasmic reticulum and transfers phosphoethanolamine (EtNP) to the first mannose of the GPI anchor. Two alternatively spliced variants, which encode an identical isoform, have been reported. [provided by RefSeq, Jul 2008]

PIGN 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=0.0016021132).

BP6

Variant 18-62154610-T-C is Benign according to our data. Variant chr18-62154610-T-C is described in ClinVar as [Benign]. Clinvar id is 403309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-62154610-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGN	NM_176787.5 linkuse as main transcript	c.484A>G	p.Lys162Glu	missense_variant	7/31	ENST00000640252.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGN	ENST00000640252.2 linkuse as main transcript	c.484A>G	p.Lys162Glu	missense_variant	7/31	1	NM_176787.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0516

AC:

7849

AN:

152054

Hom.:

251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0741

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0424

Gnomad ASJ

AF:

0.0844

Gnomad EAS

AF:

0.0767

Gnomad SAS

AF:

0.0839

Gnomad FIN

AF:

0.0340

Gnomad MID

AF:

0.137

Gnomad NFE

AF:

0.0369

Gnomad OTH

AF:

0.0612

GnomAD3 exomes

AF:

0.0518

AC:

12836

AN:

247846

Hom.:

432

AF XY:

0.0537

AC XY:

7219

AN XY:

134524

show subpopulations

Gnomad AFR exome

AF:

0.0783

Gnomad AMR exome

AF:

0.0310

Gnomad ASJ exome

AF:

0.0864

Gnomad EAS exome

AF:

0.0797

Gnomad SAS exome

AF:

0.0890

Gnomad FIN exome

AF:

0.0347

Gnomad NFE exome

AF:

0.0398

Gnomad OTH exome

AF:

0.0584

GnomAD4 exome

AF:

0.0429

AC:

61639

AN:

1435626

Hom.:

1766

Cov.:

AF XY:

0.0448

AC XY:

32040

AN XY:

715826

show subpopulations

Gnomad4 AFR exome

AF:

0.0792

Gnomad4 AMR exome

AF:

0.0321

Gnomad4 ASJ exome

AF:

0.0866

Gnomad4 EAS exome

AF:

0.0753

Gnomad4 SAS exome

AF:

0.0884

Gnomad4 FIN exome

AF:

0.0339

Gnomad4 NFE exome

AF:

0.0359

Gnomad4 OTH exome

AF:

0.0522

GnomAD4 genome

AF:

0.0517

AC:

7866

AN:

152172

Hom.:

251

Cov.:

AF XY:

0.0526

AC XY:

3916

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0742

Gnomad4 AMR

AF:

0.0423

Gnomad4 ASJ

AF:

0.0844

Gnomad4 EAS

AF:

0.0770

Gnomad4 SAS

AF:

0.0841

Gnomad4 FIN

AF:

0.0340

Gnomad4 NFE

AF:

0.0369

Gnomad4 OTH

AF:

0.0624

Alfa

AF:

0.0439

Hom.:

276

Bravo

AF:

0.0526

TwinsUK

AF:

0.0361

AC:

134

ALSPAC

AF:

0.0384

AC:

148

ESP6500AA

AF:

0.0745

AC:

273

ESP6500EA

AF:

0.0405

AC:

331

ExAC

AF:

0.0538

AC:

6503

Asia WGS

AF:

0.0710

AC:

246

AN:

3476

EpiCase

AF:

0.0451

EpiControl

AF:

0.0456

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2016

This alteration is classified as 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. -

Multiple congenital anomalies-hypotonia-seizures syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.63

Cadd

Benign

0.11

Dann

Benign

0.39

DEOGEN2

Benign

0.012

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

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.014

MetaRNN

Benign

0.0016

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

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-3.3

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

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.21

Polyphen

0.0

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

Vest4

0.017

MPC

0.027

ClinPred

0.0042

GERP RS

-2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.050

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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