chr9-35093104-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032634.4(PIGO):​c.1045T>G​(p.Ser349Ala) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S349L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

PIGO
NM_032634.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.630
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.10996008).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PIGONM_032634.4 linkuse as main transcriptc.1045T>G p.Ser349Ala missense_variant 6/11 ENST00000378617.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PIGOENST00000378617.4 linkuse as main transcriptc.1045T>G p.Ser349Ala missense_variant 6/111 NM_032634.4 P1Q8TEQ8-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Hyperphosphatasia with intellectual disability syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 04, 2022In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 540452). This variant has not been reported in the literature in individuals affected with PIGO-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 349 of the PIGO protein (p.Ser349Ala). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
15
DANN
Uncertain
0.98
DEOGEN2
Benign
0.031
.;.;T
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.48
FATHMM_MKL
Benign
0.72
D
LIST_S2
Benign
0.57
.;T;T
M_CAP
Benign
0.0068
T
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.91
L;L;L
MutationTaster
Benign
0.87
D;D;D;D
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.34
N;N;N
REVEL
Benign
0.068
Sift
Benign
0.095
T;T;T
Sift4G
Benign
0.78
T;T;T
Polyphen
0.0010
B;B;B
Vest4
0.15
MutPred
0.39
Loss of glycosylation at S349 (P = 0.0046);Loss of glycosylation at S349 (P = 0.0046);Loss of glycosylation at S349 (P = 0.0046);
MVP
0.34
MPC
0.12
ClinPred
0.097
T
GERP RS
1.8
Varity_R
0.059
gMVP
0.20

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1554673142; hg19: chr9-35093101; API