Variant summary

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

The NM_032634.4(PIGO):c.2004G>A(p.Leu668Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,614,058 control chromosomes in the GnomAD database, including 37,696 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3109 hom., cov: 33)

Exomes 𝑓: 0.21 ( 34587 hom. )

Consequence

PIGO
NM_032634.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.465

Publications

14 publications found

Variant links:

Genes affected

PIGO (HGNC:23215): (phosphatidylinositol glycan anchor biosynthesis class O) This gene encodes a protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid which contains three mannose molecules in its core backbone. The GPI-anchor is found on many blood cells and serves to anchor proteins to the cell surface. This protein is involved in the transfer of ethanolaminephosphate (EtNP) to the third mannose in GPI. At least three alternatively spliced transcripts encoding two distinct isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

PIGO Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hyperphosphatasia with intellectual disability syndrome 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Illumina, Labcorp Genetics (formerly Invitae), PanelApp Australia
hyperphosphatasia-intellectual disability syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PIGO 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=-0.46).

BP6

Variant 9-35091883-C-T is Benign according to our data. Variant chr9-35091883-C-T is described in ClinVar as Benign. ClinVar VariationId is 198601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.465 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032634.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PIGO	NM_032634.4	MANE Select	c.2004G>A	p.Leu668Leu	synonymous	Exon 7 of 11	NP_116023.2
PIGO	NM_001201484.2		c.1345-592G>A		intron	N/A	NP_001188413.1
PIGO	NM_152850.4		c.1345-592G>A		intron	N/A	NP_690577.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PIGO	ENST00000378617.4	TSL:1 MANE Select	c.2004G>A	p.Leu668Leu	synonymous	Exon 7 of 11	ENSP00000367880.3
PIGO	ENST00000298004.9	TSL:1	c.1345-592G>A		intron	N/A	ENSP00000298004.5
PIGO	ENST00000465745.6	TSL:2	n.3005G>A		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29505

AN:

152106

Hom.:

3105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.284

Gnomad EAS

AF:

0.0798

Gnomad SAS

AF:

0.275

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.198

GnomAD2 exomes

AF:

0.193

AC:

48358

AN:

251136

AF XY:

0.197

show subpopulations

Gnomad AFR exome

AF:

0.186

Gnomad AMR exome

AF:

0.166

Gnomad ASJ exome

AF:

0.278

Gnomad EAS exome

AF:

0.0833

Gnomad FIN exome

AF:

0.110

Gnomad NFE exome

AF:

0.207

Gnomad OTH exome

AF:

0.186

GnomAD4 exome

AF:

0.213

AC:

311592

AN:

1461834

Hom.:

34587

Cov.:

AF XY:

0.214

AC XY:

155571

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.180

AC:

6041

AN:

33478

American (AMR)

AF:

0.171

AC:

7659

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

7333

AN:

26134

East Asian (EAS)

AF:

0.0654

AC:

2598

AN:

39700

South Asian (SAS)

AF:

0.267

AC:

23016

AN:

86258

European-Finnish (FIN)

AF:

0.109

AC:

5809

AN:

53390

Middle Eastern (MID)

AF:

0.223

AC:

1289

AN:

5768

European-Non Finnish (NFE)

AF:

0.220

AC:

244811

AN:

1111992

Other (OTH)

AF:

0.216

AC:

13036

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

18150

36299

54449

72598

90748

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8568

17136

25704

34272

42840

<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:

0.194

AC:

29542

AN:

152224

Hom.:

3109

Cov.:

AF XY:

0.191

AC XY:

14224

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.183

AC:

7621

AN:

41548

American (AMR)

AF:

0.200

AC:

3055

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

985

AN:

3468

East Asian (EAS)

AF:

0.0798

AC:

413

AN:

5176

South Asian (SAS)

AF:

0.275

AC:

1326

AN:

4820

European-Finnish (FIN)

AF:

0.102

AC:

1084

AN:

10596

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.211

AC:

14319

AN:

68010

Other (OTH)

AF:

0.199

AC:

419

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1227

2454

3680

4907

6134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<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:

0.184

Hom.:

1501

Bravo

AF:

0.198

Asia WGS

AF:

0.169

AC:

591

AN:

3478

EpiCase

AF:

0.214

EpiControl

AF:

0.206

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hyperphosphatasia with intellectual disability syndrome 2 (3)

not specified (3)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

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