NM_032634.4:c.512-17C>T

Variant names:

• chr9-35094376-G-A
• rs2240116
• NM_032634.4:c.512-17C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032634.4(PIGO):​c.512-17C>T variant causes a 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 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.49
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hyperphosphatasia with intellectual disability syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Illumina
• hyperphosphatasia-intellectual disability syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032634.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGO	NM_032634.4	MANE Select	c.512-17C>T		intron	N/A	NP_116023.2
	PIGO	NM_001201484.2		c.512-17C>T		intron	N/A	NP_001188413.1	Q8TEQ8-2
	PIGO	NM_152850.4		c.512-17C>T		intron	N/A	NP_690577.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGO	ENST00000378617.4	TSL:1 MANE Select	c.512-17C>T		intron	N/A	ENSP00000367880.3	Q8TEQ8-1
	PIGO	ENST00000298004.9	TSL:1	c.512-17C>T		intron	N/A	ENSP00000298004.5	Q8TEQ8-2
	PIGO	ENST00000907113.1		c.512-17C>T		intron	N/A	ENSP00000577172.1

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

GnomAD2 exomes AF: 0.0898 AC: 20753 AN: 231066 AF XY: 0.0876

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 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

African (AFR) AF: 0.0575 AC: 1836 AN: 31934

American (AMR) AF: 0.130 AC: 4873 AN: 37616

Ashkenazi Jewish (ASJ) AF: 0.0880 AC: 2220 AN: 25222

East Asian (EAS) AF: 0.345 AC: 13554 AN: 39274

South Asian (SAS) AF: 0.117 AC: 9714 AN: 82788

European-Finnish (FIN) AF: 0.0772 AC: 4099 AN: 53118

Middle Eastern (MID) AF: 0.0802 AC: 457 AN: 5698

European-Non Finnish (NFE) AF: 0.0399 AC: 44155 AN: 1107028

Other (OTH) AF: 0.0719 AC: 4283 AN: 59586

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

African (AFR) AF: 0.0569 AC: 2364 AN: 41548

American (AMR) AF: 0.0796 AC: 1218 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0873 AC: 303 AN: 3472

East Asian (EAS) AF: 0.330 AC: 1707 AN: 5174

South Asian (SAS) AF: 0.128 AC: 617 AN: 4828

European-Finnish (FIN) AF: 0.0758 AC: 804 AN: 10606

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0445 AC: 3024 AN: 68024

Other (OTH) AF: 0.0695 AC: 147 AN: 2116

Alfa AF: 0.0524 Hom.: 209

Bravo AF: 0.0714

Asia WGS AF: 0.188 AC: 653 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Hyperphosphatasia with intellectual disability syndrome 2 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.76
PhyloP100		1.5
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

Other links and lift over

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