18-62147091-G-C

Position:

chr18-62147091-G-C

Variant summary

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

The NM_176787.5(PIGN):c.685C>G(p.His229Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 1,587,026 control chromosomes in the GnomAD database, including 468,501 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 48759 hom., cov: 32)

Exomes 𝑓: 0.76 ( 419742 hom. )

Consequence

PIGN
NM_176787.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.89

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.619225E-7).

BP6

Variant 18-62147091-G-C is Benign according to our data. Variant chr18-62147091-G-C is described in ClinVar as [Benign]. Clinvar id is 403308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-62147091-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGN	NM_176787.5 linkuse as main transcript	c.685C>G	p.His229Asp	missense_variant	9/31	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.685C>G	p.His229Asp	missense_variant	9/31	1	NM_176787.5	ENSP00000492233.1	O95427
PIGN	ENST00000400334.7 linkuse as main transcript	c.685C>G	p.His229Asp	missense_variant	8/30	1		ENSP00000383188.2	O95427
PIGN	ENST00000638424.1 linkuse as main transcript	n.685C>G		non_coding_transcript_exon_variant	7/29	5		ENSP00000491963.1	A0A1W2PQZ1

Frequencies

GnomAD3 genomes

AF:

0.798

AC:

121287

AN:

152032

Hom.:

48693

Cov.:

show subpopulations

Gnomad AFR

AF:

0.873

Gnomad AMI

AF:

0.706

Gnomad AMR

AF:

0.814

Gnomad ASJ

AF:

0.817

Gnomad EAS

AF:

0.909

Gnomad SAS

AF:

0.851

Gnomad FIN

AF:

0.753

Gnomad MID

AF:

0.835

Gnomad NFE

AF:

0.743

Gnomad OTH

AF:

0.792

GnomAD3 exomes

AF:

0.788

AC:

190899

AN:

242216

Hom.:

75665

AF XY:

0.786

AC XY:

103247

AN XY:

131294

show subpopulations

Gnomad AFR exome

AF:

0.873

Gnomad AMR exome

AF:

0.826

Gnomad ASJ exome

AF:

0.819

Gnomad EAS exome

AF:

0.912

Gnomad SAS exome

AF:

0.847

Gnomad FIN exome

AF:

0.745

Gnomad NFE exome

AF:

0.734

Gnomad OTH exome

AF:

0.784

GnomAD4 exome

AF:

0.762

AC:

1093869

AN:

1434876

Hom.:

419742

Cov.:

AF XY:

0.764

AC XY:

545741

AN XY:

714358

show subpopulations

Gnomad4 AFR exome

AF:

0.877

Gnomad4 AMR exome

AF:

0.826

Gnomad4 ASJ exome

AF:

0.819

Gnomad4 EAS exome

AF:

0.879

Gnomad4 SAS exome

AF:

0.845

Gnomad4 FIN exome

AF:

0.744

Gnomad4 NFE exome

AF:

0.744

Gnomad4 OTH exome

AF:

0.784

GnomAD4 genome

AF:

0.798

AC:

121409

AN:

152150

Hom.:

48759

Cov.:

AF XY:

0.799

AC XY:

59445

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.873

Gnomad4 AMR

AF:

0.814

Gnomad4 ASJ

AF:

0.817

Gnomad4 EAS

AF:

0.908

Gnomad4 SAS

AF:

0.852

Gnomad4 FIN

AF:

0.753

Gnomad4 NFE

AF:

0.743

Gnomad4 OTH

AF:

0.792

Alfa

AF:

0.763

Hom.:

14479

Bravo

AF:

0.806

TwinsUK

AF:

0.742

AC:

2753

ALSPAC

AF:

0.745

AC:

2870

ESP6500AA

AF:

0.878

AC:

3151

ESP6500EA

AF:

0.753

AC:

6121

ExAC

AF:

0.782

AC:

94288

Asia WGS

AF:

0.864

AC:

2992

AN:

3460

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Multiple congenital anomalies-hypotonia-seizures syndrome 1

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
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: Frequency -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 11, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.010

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

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.46

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

MetaRNN

Benign

9.6e-7

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

-0.98

MutationAssessor

Benign

-1.2

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

PrimateAI

Benign

0.36

PROVEAN

Benign

0.010

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

REVEL

Benign

0.082

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

Polyphen

0.0

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

Vest4

0.043

MPC

0.027

ClinPred

0.00068

GERP RS

3.7

Varity_R

0.10

gMVP

0.35

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