rs2298784

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_176787.5(PIGN):c.1488A>G(p.Ala496=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0061 in 1,613,146 control chromosomes in the GnomAD database, including 283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 45 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 238 hom. )

Consequence

PIGN
NM_176787.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0200

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 18-62109920-T-C is Benign according to our data. Variant chr18-62109920-T-C is described in ClinVar as [Benign]. Clinvar id is 472211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0629 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.1488A>G	p.Ala496=	synonymous_variant	17/31	ENST00000640252.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGN	ENST00000640252.2 linkuse as main transcript	c.1488A>G	p.Ala496=	synonymous_variant	17/31	1	NM_176787.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00967

AC:

1470

AN:

151972

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00288

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000787

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.0689

Gnomad SAS

AF:

0.00663

Gnomad FIN

AF:

0.0694

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00281

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.0125

AC:

3110

AN:

248676

Hom.:

AF XY:

0.0124

AC XY:

1669

AN XY:

134884

show subpopulations

Gnomad AFR exome

AF:

0.00252

Gnomad AMR exome

AF:

0.000522

Gnomad ASJ exome

AF:

0.00378

Gnomad EAS exome

AF:

0.0628

Gnomad SAS exome

AF:

0.00248

Gnomad FIN exome

AF:

0.0654

Gnomad NFE exome

AF:

0.00289

Gnomad OTH exome

AF:

0.0131

GnomAD4 exome

AF:

0.00573

AC:

8369

AN:

1461056

Hom.:

238

Cov.:

AF XY:

0.00563

AC XY:

4094

AN XY:

726808

show subpopulations

Gnomad4 AFR exome

AF:

0.00221

Gnomad4 AMR exome

AF:

0.000627

Gnomad4 ASJ exome

AF:

0.00429

Gnomad4 EAS exome

AF:

0.0719

Gnomad4 SAS exome

AF:

0.00274

Gnomad4 FIN exome

AF:

0.0629

Gnomad4 NFE exome

AF:

0.00113

Gnomad4 OTH exome

AF:

0.00738

GnomAD4 genome

AF:

0.00966

AC:

1469

AN:

152090

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

971

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00287

Gnomad4 AMR

AF:

0.000786

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.0688

Gnomad4 SAS

AF:

0.00684

Gnomad4 FIN

AF:

0.0694

Gnomad4 NFE

AF:

0.00281

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.00239

Hom.:

Bravo

AF:

0.00435

Asia WGS

AF:

0.0330

AC:

114

AN:

3478

EpiCase

AF:

0.000982

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 26, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 18, 2017	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

Cadd

Benign

8.1

Dann

Benign

0.75

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