rs41274877

chr9-35091847-C-Gchr9-35091847-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_032634.4(PIGO):c.2040G>C(p.Leu680=) 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 (★★). Synonymous variant affecting the same amino acid position (i.e. L680L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0051 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0070 (43 hom.)
• Consequence: PIGO NM_032634.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.142

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]

ACMG classification

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. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGO	NM_032634.4	c.2040G>C	p.Leu680=	synonymous_variant	7/11	ENST00000378617.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGO	ENST00000378617.4	c.2040G>C	p.Leu680=	synonymous_variant	7/11	1	NM_032634.4	P1

Frequencies

GnomAD3 genomes AF: 0.00512 AC: 779 AN: 152222 Hom.: 2 Cov.: 32

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.: 10 AF XY: 0.00531 AC XY: 720 AN XY: 135684

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.: 43 Cov.: 31 AF XY: 0.00692 AC XY: 5032 AN XY: 727180

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.: 2 Cov.: 32 AF XY: 0.00466 AC XY: 347 AN XY: 74486

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.: 3

Bravo AF: 0.00619

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0103

EpiControl AF: 0.00931

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 27, 2017	- -

Hyperphosphatasia with intellectual disability syndrome 2 Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 28, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	PIGO: BP4, BP7, BS2 -

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

Other links and lift over

dbSNP: rs41274877; hg19: chr9-35091844; COSMIC: COSV99957115; COSMIC: COSV99957115;