rs35287398

Positions:

chr9-35092483-T-G

Variant summary

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

The NM_032634.4(PIGO):c.1404A>C(p.Ala468=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 1,614,142 control chromosomes in the GnomAD database, including 235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 19 hom., cov: 33)

Exomes 𝑓: 0.015 ( 216 hom. )

Consequence

PIGO
NM_032634.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.304

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 9-35092483-T-G is Benign according to our data. Variant chr9-35092483-T-G is described in ClinVar as [Benign]. Clinvar id is 262095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.304 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0125 (1910/152296) while in subpopulation SAS AF= 0.0216 (104/4822). AF 95% confidence interval is 0.0182. There are 19 homozygotes in gnomad4. There are 944 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGO	NM_032634.4 linkuse as main transcript	c.1404A>C	p.Ala468=	synonymous_variant	7/11	ENST00000378617.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGO	ENST00000378617.4 linkuse as main transcript	c.1404A>C	p.Ala468=	synonymous_variant	7/11	1	NM_032634.4	P1	Q8TEQ8-1

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1903

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00572

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00942

Gnomad ASJ

AF:

0.0380

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0211

Gnomad FIN

AF:

0.0183

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0155

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.0145

AC:

3625

AN:

250786

Hom.:

AF XY:

0.0154

AC XY:

2092

AN XY:

135532

show subpopulations

Gnomad AFR exome

AF:

0.00511

Gnomad AMR exome

AF:

0.00876

Gnomad ASJ exome

AF:

0.0321

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0224

Gnomad FIN exome

AF:

0.0162

Gnomad NFE exome

AF:

0.0155

Gnomad OTH exome

AF:

0.0199

GnomAD4 exome

AF:

0.0145

AC:

21214

AN:

1461846

Hom.:

216

Cov.:

AF XY:

0.0153

AC XY:

11094

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00633

Gnomad4 AMR exome

AF:

0.0102

Gnomad4 ASJ exome

AF:

0.0335

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0247

Gnomad4 FIN exome

AF:

0.0155

Gnomad4 NFE exome

AF:

0.0140

Gnomad4 OTH exome

AF:

0.0160

GnomAD4 genome

AF:

0.0125

AC:

1910

AN:

152296

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

944

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00575

Gnomad4 AMR

AF:

0.00941

Gnomad4 ASJ

AF:

0.0380

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0216

Gnomad4 FIN

AF:

0.0183

Gnomad4 NFE

AF:

0.0155

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0153

Hom.:

Bravo

AF:

0.0114

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0204

EpiControl

AF:

0.0196

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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 07, 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. -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 23, 2017	- -

Hyperphosphatasia with intellectual disability syndrome 2

Benign:2

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

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

-0.79

CADD

Benign

6.5

DANN

Benign

0.67

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