NM_032634.4:c.2198G>C

Variant names:

• chr9-35091689-C-G
• NM_032634.4:c.2198G>C

Variant summary

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

The NM_032634.4(PIGO):​c.2198G>C​(p.Arg733Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,290 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R733Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PIGO NM_032634.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.594

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 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 rank	MANE	Protein	UniProt
PIGO	NM_032634.4	c.2198G>C	p.Arg733Pro	missense_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.2198G>C	p.Arg733Pro	missense_variant	Exon 7 of 11	1	NM_032634.4	ENSP00000367880.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460290 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726500

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.29
Sift	Benign	0.28	T
Sift4G	Benign	0.30	T
Polyphen		0.84	P
Vest4		0.58
MutPred		0.51		Gain of loop (P = 0.0079);
MVP		0.55
MPC		0.42
ClinPred		0.50	T
GERP RS		2.5
Varity_R		0.37
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-35091686;