Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_176787.5(PIGN):c.1749G>A(p.Arg583Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000051 in 1,606,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R583R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

PIGN
NM_176787.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.00200

Publications

0 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 18-62106807-C-T is Benign according to our data. Variant chr18-62106807-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 539557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.002 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176787.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PIGN	NM_176787.5	MANE Select	c.1749G>A	p.Arg583Arg	synonymous	Exon 19 of 31	NP_789744.1
PIGN	NM_001438896.1		c.1749G>A	p.Arg583Arg	synonymous	Exon 19 of 32	NP_001425825.1
PIGN	NM_012327.6		c.1749G>A	p.Arg583Arg	synonymous	Exon 18 of 30	NP_036459.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PIGN	ENST00000640252.2	TSL:1 MANE Select	c.1749G>A	p.Arg583Arg	synonymous	Exon 19 of 31	ENSP00000492233.1
PIGN	ENST00000400334.7	TSL:1	c.1749G>A	p.Arg583Arg	synonymous	Exon 18 of 30	ENSP00000383188.2
PIGN	ENST00000638424.1	TSL:5	n.1749G>A		non_coding_transcript_exon	Exon 17 of 29	ENSP00000491963.1

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000918

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000633

AC:

AN:

237056

AF XY:

0.0000234

show subpopulations

Gnomad AFR exome

AF:

0.000907

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000938

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.0000268

AC:

AN:

1454340

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

722588

show subpopulations

African (AFR)

AF:

0.000840

AC:

AN:

33336

American (AMR)

AF:

0.00

AC:

AN:

43970

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25944

East Asian (EAS)

AF:

0.00

AC:

AN:

39410

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84544

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52942

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000451

AC:

AN:

1108284

Other (OTH)

AF:

0.0000831

AC:

AN:

60150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000282

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.000915

AC:

AN:

41538

American (AMR)

AF:

0.000131

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000230

Hom.:

Bravo

AF:

0.000366

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Inborn genetic diseases (1)

Multiple congenital anomalies-hypotonia-seizures syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

3.6

(source)

DANN

Benign

0.47

PhyloP100

-0.0020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over