rs35287398

Variant names:

• chr9-35092483-T-G
• rs35287398
• NM_032634.4:c.1404A>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_032634.4(PIGO):​c.1404A>C​(p.Ala468Ala) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.304

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGO	NM_032634.4	c.1404A>C	p.Ala468Ala	synonymous_variant	Exon 7 of 11	ENST00000378617.4	NP_116023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGO	ENST00000378617.4	c.1404A>C	p.Ala468Ala	synonymous_variant	Exon 7 of 11	1	NM_032634.4	ENSP00000367880.3

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1903 AN: 152178 Hom.: 19 Cov.: 33

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

GnomAD2 exomes AF: 0.0145 AC: 3625 AN: 250786 AF XY: 0.0154

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 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.: 33 AF XY: 0.0153 AC XY: 11094 AN XY: 727214

Gnomad4 AFR exome AF: 0.00633 AC: 212 AN: 33480

Gnomad4 AMR exome AF: 0.0102 AC: 458 AN: 44724

Gnomad4 ASJ exome AF: 0.0335 AC: 875 AN: 26136

Gnomad4 EAS exome AF: 0.000176 AC: 7 AN: 39700

Gnomad4 SAS exome AF: 0.0247 AC: 2129 AN: 86258

Gnomad4 FIN exome AF: 0.0155 AC: 830 AN: 53414

Gnomad4 NFE exome AF: 0.0140 AC: 15523 AN: 1111976

Gnomad4 Remaining exome AF: 0.0160 AC: 965 AN: 60390

GnomAD4 genome AF: 0.0125 AC: 1910 AN: 152296 Hom.: 19 Cov.: 33 AF XY: 0.0127 AC XY: 944 AN XY: 74464

Gnomad4 AFR AF: 0.00575 AC: 0.00575183 AN: 0.00575183

Gnomad4 AMR AF: 0.00941 AC: 0.00940562 AN: 0.00940562

Gnomad4 ASJ AF: 0.0380 AC: 0.0380184 AN: 0.0380184

Gnomad4 EAS AF: 0.000386 AC: 0.0003861 AN: 0.0003861

Gnomad4 SAS AF: 0.0216 AC: 0.0215678 AN: 0.0215678

Gnomad4 FIN AF: 0.0183 AC: 0.0182846 AN: 0.0182846

Gnomad4 NFE AF: 0.0155 AC: 0.0155079 AN: 0.0155079

Gnomad4 OTH AF: 0.0147 AC: 0.0146641 AN: 0.0146641

Alfa AF: 0.0153 Hom.: 10

Bravo AF: 0.0114

Asia WGS AF: 0.0190 AC: 67 AN: 3478

EpiCase AF: 0.0204

EpiControl AF: 0.0196

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 23, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 07, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.5
DANN	Benign	0.67
Mutation Taster		=100/0	polymorphism (auto)

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: rs35287398; hg19: chr9-35092480; COSMIC: COSV53054552; COSMIC: COSV53054552;