9-35089131-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032634.4(PIGO):c.3231C>G(p.Ser1077Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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. S1077T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PIGO NM_032634.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22861758).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGO	NM_032634.4	c.3231C>G	p.Ser1077Arg	missense_variant	11/11	ENST00000378617.4
PIGO	NM_001201484.2	c.1980C>G	p.Ser660Arg	missense_variant	13/13
PIGO	NM_152850.4	c.1980C>G	p.Ser660Arg	missense_variant	12/12
PIGO	XM_005251619.4	c.3231C>G	p.Ser1077Arg	missense_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGO	ENST00000378617.4	c.3231C>G	p.Ser1077Arg	missense_variant	11/11	1	NM_032634.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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	Uncertain	0.36
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	21
Dann	Uncertain	0.99
Eigen	Benign	-0.051
Eigen_PC	Benign	0.058
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.86	D;D;N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.10	T;T;T
Sift4G	Benign	0.15	T;T;T
Polyphen		0.40	B;B;B
Vest4		0.52
MutPred		0.52		.;.;Gain of MoRF binding (P = 0.0106);
MVP		0.65
MPC		0.31
ClinPred		0.69	D
GERP RS		3.5
Varity_R		0.082
gMVP		0.57

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: rs766677182; hg19: chr9-35089128;