rs41274877

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_032634.4(PIGO):c.2040G>C(p.Leu680Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00679 in 1,614,096 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0070 ( 43 hom. )

Consequence

PIGO
NM_032634.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.142

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 links:

PIGO (HGNC:):

PIGO links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 9-35091847-C-G is Benign according to our data. Variant chr9-35091847-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 262096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.142 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00511 (779/152338) while in subpopulation NFE AF= 0.00725 (493/68038). AF 95% confidence interval is 0.00672. There are 2 homozygotes in gnomad4. There are 347 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGO	NM_032634.4 linkuse as main transcript	c.2040G>C	p.Leu680Leu	synonymous_variant	7/11	ENST00000378617.4	NP_116023.2	Q8TEQ8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGO	ENST00000378617.4 linkuse as main transcript	c.2040G>C	p.Leu680Leu	synonymous_variant	7/11	1	NM_032634.4	ENSP00000367880.3		Q8TEQ8-1

Frequencies

GnomAD3 genomes

AF:

0.00512

AC:

779

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00725

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.00541

AC:

1356

AN:

250634

Hom.:

AF XY:

0.00531

AC XY:

720

AN XY:

135684

show subpopulations

Gnomad AFR exome

AF:

0.000991

Gnomad AMR exome

AF:

0.00515

Gnomad ASJ exome

AF:

0.0313

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00686

Gnomad OTH exome

AF:

0.00800

GnomAD4 exome

AF:

0.00696

AC:

10175

AN:

1461758

Hom.:

Cov.:

AF XY:

0.00692

AC XY:

5032

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00588

Gnomad4 ASJ exome

AF:

0.0322

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000823

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.00757

Gnomad4 OTH exome

AF:

0.00825

GnomAD4 genome

AF:

0.00511

AC:

779

AN:

152338

Hom.:

Cov.:

AF XY:

0.00466

AC XY:

347

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00634

Gnomad4 ASJ

AF:

0.0308

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00725

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.00981

Hom.:

Bravo

AF:

0.00619

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0103

EpiControl

AF:

0.00931

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 28, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	PIGO: BP4, BP7, BS2 -

Hyperphosphatasia with intellectual disability syndrome 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Mar 27, 2017

- -

PIGO-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 06, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.89

DANN

Benign

0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over