chr18-62106804-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_176787.5(PIGN):c.1752G>A(p.Leu584Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,603,330 control chromosomes in the GnomAD database, including 42,752 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2934 hom., cov: 32)

Exomes 𝑓: 0.22 ( 39818 hom. )

Consequence

PIGN
NM_176787.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.250

Publications

19 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 18-62106804-C-T is Benign according to our data. Variant chr18-62106804-C-T is described in ClinVar as Benign. ClinVar VariationId is 403302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.25 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.1752G>A	p.Leu584Leu	synonymous_variant	Exon 19 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.1752G>A	p.Leu584Leu	synonymous_variant	Exon 19 of 31	1	NM_176787.5	ENSP00000492233.1	O95427
PIGN	ENST00000400334.7 link	c.1752G>A	p.Leu584Leu	synonymous_variant	Exon 18 of 30	1		ENSP00000383188.2	O95427
PIGN	ENST00000638424.1 link	n.1752G>A		non_coding_transcript_exon_variant	Exon 17 of 29	5		ENSP00000491963.1	A0A1W2PQZ1

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25729

AN:

152074

Hom.:

2933

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0444

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.00501

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.280

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.192

GnomAD2 exomes

AF:

0.173

AC:

40731

AN:

234998

AF XY:

0.176

show subpopulations

Gnomad AFR exome

AF:

0.0397

Gnomad AMR exome

AF:

0.106

Gnomad ASJ exome

AF:

0.253

Gnomad EAS exome

AF:

0.00283

Gnomad FIN exome

AF:

0.237

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.205

GnomAD4 exome

AF:

0.225

AC:

326239

AN:

1451138

Hom.:

39818

Cov.:

AF XY:

0.223

AC XY:

160565

AN XY:

720926

show subpopulations

African (AFR)

AF:

0.0379

AC:

1261

AN:

33310

American (AMR)

AF:

0.113

AC:

4928

AN:

43804

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

6442

AN:

25924

East Asian (EAS)

AF:

0.00140

AC:

AN:

39378

South Asian (SAS)

AF:

0.114

AC:

9616

AN:

84428

European-Finnish (FIN)

AF:

0.235

AC:

12423

AN:

52814

Middle Eastern (MID)

AF:

0.242

AC:

1392

AN:

5746

European-Non Finnish (NFE)

AF:

0.251

AC:

277631

AN:

1105710

Other (OTH)

AF:

0.208

AC:

12491

AN:

60024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

11573

23147

34720

46294

57867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9176

18352

27528

36704

45880

<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:

0.169

AC:

25734

AN:

152192

Hom.:

2934

Cov.:

AF XY:

0.167

AC XY:

12390

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0443

AC:

1840

AN:

41554

American (AMR)

AF:

0.152

AC:

2319

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

869

AN:

3472

East Asian (EAS)

AF:

0.00521

AC:

AN:

5182

South Asian (SAS)

AF:

0.108

AC:

520

AN:

4822

European-Finnish (FIN)

AF:

0.246

AC:

2597

AN:

10574

Middle Eastern (MID)

AF:

0.277

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.248

AC:

16846

AN:

67982

Other (OTH)

AF:

0.194

AC:

410

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1027

2055

3082

4110

5137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<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:

0.222

Hom.:

6663

Bravo

AF:

0.157

Asia WGS

AF:

0.0810

AC:

283

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.37

CADD

Benign

3.2

(source)

DANN

Benign

0.59

PhyloP100

0.25

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