rs2298784

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.1488A>G(p.Ala496Ala) 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

Publications

4 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=-0.75).

BP6

Variant 18-62109920-T-C is Benign according to our data. Variant chr18-62109920-T-C is described in ClinVar as Benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
PIGN	NM_176787.5 link	c.1488A>G	p.Ala496Ala	synonymous_variant	Exon 17 of 31	ENST00000640252.2	NP_789744.1	O95427A0A024R2C3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PIGN	ENST00000640252.2 link	c.1488A>G	p.Ala496Ala	synonymous_variant	Exon 17 of 31	1	NM_176787.5	ENSP00000492233.1	O95427
PIGN	ENST00000400334.7 link	c.1488A>G	p.Ala496Ala	synonymous_variant	Exon 16 of 30	1		ENSP00000383188.2	O95427
PIGN	ENST00000638424.1 link	n.1488A>G		non_coding_transcript_exon_variant	Exon 15 of 29	5		ENSP00000491963.1	A0A1W2PQZ1

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

GnomAD2 exomes

AF:

0.0125

AC:

3110

AN:

248676

AF XY:

0.0124

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 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

African (AFR)

AF:

0.00221

AC:

AN:

33448

American (AMR)

AF:

0.000627

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00429

AC:

112

AN:

26122

East Asian (EAS)

AF:

0.0719

AC:

2849

AN:

39606

South Asian (SAS)

AF:

0.00274

AC:

236

AN:

86236

European-Finnish (FIN)

AF:

0.0629

AC:

3357

AN:

53384

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00113

AC:

1260

AN:

1111470

Other (OTH)

AF:

0.00738

AC:

445

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

428

856

1284

1712

2140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<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:

0.00966

AC:

1469

AN:

152090

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

971

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00287

AC:

119

AN:

41506

American (AMR)

AF:

0.000786

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.0688

AC:

356

AN:

5172

South Asian (SAS)

AF:

0.00684

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0694

AC:

734

AN:

10572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00281

AC:

191

AN:

67962

Other (OTH)

AF:

0.00711

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

134

201

268

335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00235

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

Jul 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 18, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Aug 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 02, 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

-0.75

CADD

Benign

8.1

(source)

DANN

Benign

0.75

PhyloP100

-0.020

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

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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