chr9-35091654-G-C

Position:

• chr9-35091654-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032634.4(PIGO):​c.2233C>G​(p.Arg745Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PIGO NM_032634.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.581

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGO	NM_032634.4	c.2233C>G	p.Arg745Gly	missense_variant	7/11	ENST00000378617.4	NP_116023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGO	ENST00000378617.4	c.2233C>G	p.Arg745Gly	missense_variant	7/11	1	NM_032634.4	ENSP00000367880.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248066 Hom.: 0 AF XY: 0.00000742 AC XY: 1 AN XY: 134858

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000895

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.60
MutPred		0.55		Gain of catalytic residue at R745 (P = 0.0176);
MVP		0.60
MPC		0.72
ClinPred		0.90	D
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.82

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: rs762428877; hg19: chr9-35091651;