rs12326381

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_176787.5(PIGN):c.1962G>A(p.Leu654Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,456,732 control chromosomes in the GnomAD database, including 36,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2947 hom., cov: 31)

Exomes 𝑓: 0.22 ( 33565 hom. )

Consequence

PIGN
NM_176787.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.52

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

multiple congenital anomalies-hypotonia-seizures syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet, ClinGen, PanelApp Australia
Fryns syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PIGN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 18-62102800-C-T is Benign according to our data. Variant chr18-62102800-C-T is described in ClinVar as Benign. ClinVar VariationId is 403301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.52 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGN	NM_176787.5 link	c.1962G>A	p.Leu654Leu	synonymous_variant	Exon 21 of 31	ENST00000640252.2	NP_789744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
PIGN	ENST00000640252.2 link	c.1962G>A	p.Leu654Leu	synonymous_variant	Exon 21 of 31	1	NM_176787.5	ENSP00000492233.1
PIGN	ENST00000400334.7 link	c.1962G>A	p.Leu654Leu	synonymous_variant	Exon 20 of 30	1		ENSP00000383188.2
PIGN	ENST00000638424.1 link	n.1962G>A		non_coding_transcript_exon_variant	Exon 19 of 29	5		ENSP00000491963.1

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25968

AN:

152014

Hom.:

2946

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0499

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.00501

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.245

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.192

GnomAD2 exomes

AF:

0.166

AC:

29527

AN:

177866

AF XY:

0.166

show subpopulations

Gnomad AFR exome

AF:

0.0406

Gnomad AMR exome

AF:

0.0996

Gnomad ASJ exome

AF:

0.248

Gnomad EAS exome

AF:

0.00272

Gnomad FIN exome

AF:

0.232

Gnomad NFE exome

AF:

0.226

Gnomad OTH exome

AF:

0.197

GnomAD4 exome

AF:

0.217

AC:

283249

AN:

1304598

Hom.:

33565

Cov.:

AF XY:

0.216

AC XY:

140140

AN XY:

649912

show subpopulations

African (AFR)

AF:

0.0401

AC:

1203

AN:

30008

American (AMR)

AF:

0.111

AC:

3954

AN:

35746

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

5974

AN:

24448

East Asian (EAS)

AF:

0.00140

AC:

AN:

37144

South Asian (SAS)

AF:

0.111

AC:

8348

AN:

75418

European-Finnish (FIN)

AF:

0.234

AC:

11831

AN:

50592

Middle Eastern (MID)

AF:

0.239

AC:

1310

AN:

5484

European-Non Finnish (NFE)

AF:

0.242

AC:

239404

AN:

990544

Other (OTH)

AF:

0.202

AC:

11173

AN:

55214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

8748

17496

26244

34992

43740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7716

15432

23148

30864

38580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.171

AC:

25975

AN:

152134

Hom.:

2947

Cov.:

AF XY:

0.168

AC XY:

12491

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0497

AC:

2065

AN:

41526

American (AMR)

AF:

0.152

AC:

2327

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

869

AN:

3468

East Asian (EAS)

AF:

0.00521

AC:

AN:

5182

South Asian (SAS)

AF:

0.108

AC:

520

AN:

4814

European-Finnish (FIN)

AF:

0.245

AC:

2595

AN:

10582

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.248

AC:

16852

AN:

67970

Other (OTH)

AF:

0.194

AC:

409

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1035

2070

3105

4140

5175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.236

Hom.:

7529

Bravo

AF:

0.159

Asia WGS

AF:

0.0800

AC:

280

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 -

Inborn genetic diseases

Benign:1

Mar 19, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.36

(source)

DANN

Benign

0.45

PhyloP100

-2.5

PromoterAI

-0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over