rs2240116

chr9-35094376-G-Achr9-35094376-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032634.4(PIGO):c.512-17C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0598 in 1,594,534 control chromosomes in the GnomAD database, including 5,463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.067 (601 hom., cov: 32)
  • Exomes 𝑓: 0.059 (4862 hom.)
• Consequence: PIGO NM_032634.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.49

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 9-35094376-G-A is Benign according to our data. Variant chr9-35094376-G-A is described in ClinVar as [Benign]. Clinvar id is 262100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGO	NM_032634.4	c.512-17C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000378617.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGO	ENST00000378617.4	c.512-17C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_032634.4	P1

Frequencies

GnomAD3 genomes AF: 0.0672 AC: 10224 AN: 152152 Hom.: 600 Cov.: 32

Gnomad AFR AF: 0.0570

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.0794

Gnomad ASJ AF: 0.0873

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0758

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0445

Gnomad OTH AF: 0.0702

GnomAD3 exomes AF: 0.0898 AC: 20753 AN: 231066 Hom.: 1655 AF XY: 0.0876 AC XY: 11002 AN XY: 125662

Gnomad AFR exome AF: 0.0530

Gnomad AMR exome AF: 0.137

Gnomad ASJ exome AF: 0.0822

Gnomad EAS exome AF: 0.335

Gnomad SAS exome AF: 0.114

Gnomad FIN exome AF: 0.0761

Gnomad NFE exome AF: 0.0433

Gnomad OTH exome AF: 0.0737

GnomAD4 exome AF: 0.0591 AC: 85191 AN: 1442264 Hom.: 4862 Cov.: 32 AF XY: 0.0612 AC XY: 43908 AN XY: 717684

Gnomad4 AFR exome AF: 0.0575

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.0880

Gnomad4 EAS exome AF: 0.345

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.0772

Gnomad4 NFE exome AF: 0.0399

Gnomad4 OTH exome AF: 0.0719

GnomAD4 genome AF: 0.0672 AC: 10227 AN: 152270 Hom.: 601 Cov.: 32 AF XY: 0.0715 AC XY: 5322 AN XY: 74448

Gnomad4 AFR AF: 0.0569

Gnomad4 AMR AF: 0.0796

Gnomad4 ASJ AF: 0.0873

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.0758

Gnomad4 NFE AF: 0.0445

Gnomad4 OTH AF: 0.0695

Alfa AF: 0.0513 Hom.: 120

Bravo AF: 0.0714

Asia WGS AF: 0.188 AC: 653 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 09, 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:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	14
Dann	Benign	0.76

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: rs2240116; hg19: chr9-35094373; COSMIC: COSV53052510; COSMIC: COSV53052510;