rs200658159

Positions:

chr18-62090521-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_176787.5(PIGN):c.2238A>G(p.Ile746Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,611,218 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 5 hom. )

Consequence

PIGN
NM_176787.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.108

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:

PIGN (HGNC:):

PIGN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006445229).

BP6

Variant 18-62090521-T-C is Benign according to our data. Variant chr18-62090521-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 539565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-62090521-T-C is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGN	NM_176787.5 linkuse as main transcript	c.2238A>G	p.Ile746Met	missense_variant	24/31	ENST00000640252.2	NP_789744.1	O95427A0A024R2C3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PIGN	ENST00000640252.2 linkuse as main transcript	c.2238A>G	p.Ile746Met	missense_variant	24/31	1	NM_176787.5	ENSP00000492233.1	O95427
PIGN	ENST00000400334.7 linkuse as main transcript	c.2238A>G	p.Ile746Met	missense_variant	23/30	1		ENSP00000383188.2	O95427
PIGN	ENST00000638424.1 linkuse as main transcript	n.2238A>G		non_coding_transcript_exon_variant	22/29	5		ENSP00000491963.1	A0A1W2PQZ1

Frequencies

GnomAD3 genomes

AF:

0.00113

AC:

172

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00135

AC:

333

AN:

247046

Hom.:

AF XY:

0.00144

AC XY:

193

AN XY:

134068

show subpopulations

Gnomad AFR exome

AF:

0.000195

Gnomad AMR exome

AF:

0.000294

Gnomad ASJ exome

AF:

0.0179

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.00167

GnomAD4 exome

AF:

0.00120

AC:

1754

AN:

1458906

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

901

AN XY:

725768

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000360

Gnomad4 ASJ exome

AF:

0.0173

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00106

Gnomad4 OTH exome

AF:

0.00171

GnomAD4 genome

AF:

0.00113

AC:

172

AN:

152312

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00129

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00200

Hom.:

Bravo

AF:

0.00131

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000827

AC:

ESP6500EA

AF:

0.00282

AC:

ExAC

AF:

0.00123

AC:

149

EpiCase

AF:

0.00192

EpiControl

AF:

0.00190

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2021	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	PIGN: PM5, BP4, BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 26, 2018	- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 27, 2018

This alteration is classified as likely 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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.013

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

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.81

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

M_CAP

Benign

0.0084

MetaRNN

Benign

0.0064

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.76

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

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.18

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

REVEL

Benign

0.10

Sift

Benign

0.33

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

Sift4G

Benign

0.42

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

Polyphen

0.0020

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

Vest4

0.23

MVP

0.51

MPC

0.024

ClinPred

0.0041

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.047

gMVP

0.22

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