rs2298314

Positions:

chr9-35089406-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_032634.4(PIGO):c.3114C>T(p.Leu1038Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 1,614,158 control chromosomes in the GnomAD database, including 2,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 260 hom., cov: 33)

Exomes 𝑓: 0.028 ( 2109 hom. )

Consequence

PIGO
NM_032634.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.51

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 9-35089406-G-A is Benign according to our data. Variant chr9-35089406-G-A is described in ClinVar as [Benign]. Clinvar id is 262097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGO	NM_032634.4 linkuse as main transcript	c.3114C>T	p.Leu1038Leu	synonymous_variant	10/11	ENST00000378617.4	NP_116023.2	Q8TEQ8-1
PIGO	NM_001201484.2 linkuse as main transcript	c.1863C>T	p.Leu621Leu	synonymous_variant	12/13		NP_001188413.1	Q8TEQ8-2
PIGO	NM_152850.4 linkuse as main transcript	c.1863C>T	p.Leu621Leu	synonymous_variant	11/12		NP_690577.2	Q8TEQ8-2
PIGO	XM_005251619.4 linkuse as main transcript	c.3114C>T	p.Leu1038Leu	synonymous_variant	10/11		XP_005251676.1	Q8TEQ8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGO	ENST00000378617.4 linkuse as main transcript	c.3114C>T	p.Leu1038Leu	synonymous_variant	10/11	1	NM_032634.4	ENSP00000367880.3		Q8TEQ8-1

Frequencies

GnomAD3 genomes

AF:

0.0315

AC:

4794

AN:

152172

Hom.:

262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0178

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0224

Gnomad ASJ

AF:

0.0496

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.0646

Gnomad FIN

AF:

0.0448

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0179

Gnomad OTH

AF:

0.0310

GnomAD3 exomes

AF:

0.0469

AC:

11787

AN:

251430

Hom.:

980

AF XY:

0.0461

AC XY:

6263

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.0162

Gnomad AMR exome

AF:

0.0149

Gnomad ASJ exome

AF:

0.0505

Gnomad EAS exome

AF:

0.301

Gnomad SAS exome

AF:

0.0556

Gnomad FIN exome

AF:

0.0489

Gnomad NFE exome

AF:

0.0175

Gnomad OTH exome

AF:

0.0350

GnomAD4 exome

AF:

0.0276

AC:

40319

AN:

1461868

Hom.:

2109

Cov.:

AF XY:

0.0288

AC XY:

20921

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0171

Gnomad4 AMR exome

AF:

0.0158

Gnomad4 ASJ exome

AF:

0.0528

Gnomad4 EAS exome

AF:

0.276

Gnomad4 SAS exome

AF:

0.0570

Gnomad4 FIN exome

AF:

0.0456

Gnomad4 NFE exome

AF:

0.0149

Gnomad4 OTH exome

AF:

0.0410

GnomAD4 genome

AF:

0.0314

AC:

4786

AN:

152290

Hom.:

260

Cov.:

AF XY:

0.0347

AC XY:

2585

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0177

Gnomad4 AMR

AF:

0.0224

Gnomad4 ASJ

AF:

0.0496

Gnomad4 EAS

AF:

0.279

Gnomad4 SAS

AF:

0.0649

Gnomad4 FIN

AF:

0.0448

Gnomad4 NFE

AF:

0.0179

Gnomad4 OTH

AF:

0.0302

Alfa

AF:

0.0205

Hom.:

Bravo

AF:

0.0299

Asia WGS

AF:

0.156

AC:

542

AN:

3478

EpiCase

AF:

0.0220

EpiControl

AF:

0.0206

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 12, 2017	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 18, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Hyperphosphatasia with intellectual disability syndrome 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

6.9

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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