NM_032634.4:c.*251C>T

Variant names:

• chr9-35088841-G-A
• rs981140184
• NM_032634.4:c.*251C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032634.4(PIGO):​c.*251C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 419,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: PIGO NM_032634.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.13
• Publications: 0 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, PanelApp Australia, Labcorp Genetics (formerly Invitae), Illumina
• hyperphosphatasia-intellectual disability syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.*251C>T		3_prime_UTR	Exon 11 of 11	NP_116023.2
	PIGO	NM_001201484.2		c.*251C>T		3_prime_UTR	Exon 13 of 13	NP_001188413.1	Q8TEQ8-2
	PIGO	NM_152850.4		c.*251C>T		3_prime_UTR	Exon 12 of 12	NP_690577.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGO	ENST00000378617.4	TSL:1 MANE Select	c.*251C>T		3_prime_UTR	Exon 11 of 11	ENSP00000367880.3	Q8TEQ8-1
	PIGO	ENST00000298004.9	TSL:1	c.*251C>T		3_prime_UTR	Exon 13 of 13	ENSP00000298004.5	Q8TEQ8-2
	PIGO	ENST00000907113.1		c.*251C>T		3_prime_UTR	Exon 11 of 11	ENSP00000577172.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152066 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000375 AC: 10 AN: 266952 Hom.: 0 Cov.: 4 AF XY: 0.0000285 AC XY: 4 AN XY: 140318

African (AFR) AF: 0.00 AC: 0 AN: 8292

American (AMR) AF: 0.00 AC: 0 AN: 10702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7846

East Asian (EAS) AF: 0.00 AC: 0 AN: 15878

South Asian (SAS) AF: 0.0000343 AC: 1 AN: 29188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13800

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1174

European-Non Finnish (NFE) AF: 0.0000545 AC: 9 AN: 165074

Other (OTH) AF: 0.00 AC: 0 AN: 14998

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152066 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74260

African (AFR) AF: 0.0000483 AC: 2 AN: 41382

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.0000642

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Hyperphosphatasia with intellectual disability syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.56
DANN	Benign	0.49
PhyloP100		-3.1

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: rs981140184; hg19: chr9-35088838;