4-539296-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001127178.3(PIGG):​c.2879T>G​(p.Met960Arg) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

PIGG
NM_001127178.3 missense

Scores

2
13
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.32
Variant links:
Genes affected
PIGG (HGNC:25985): (phosphatidylinositol glycan anchor biosynthesis class G (EMM blood group)) This gene encodes an enzyme involved in glycosylphosphatidylinositol-anchor biosynthesis. The encoded protein, which is localized to the endoplasmic reticulum, is involved in transferring ethanoloamine phosphate to mannose 2 of glycosylphosphatidylinositol species H7 to form species H8. Allelic variants of this gene have been associated with intellectual disability, hypotonia, and early-onset seizures. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.863

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PIGGNM_001127178.3 linkc.2879T>G p.Met960Arg missense_variant Exon 13 of 13 ENST00000453061.7 NP_001120650.1 Q5H8A4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PIGGENST00000453061.7 linkc.2879T>G p.Met960Arg missense_variant Exon 13 of 13 1 NM_001127178.3 ENSP00000415203.2 Q5H8A4-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.54
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.082
.;T;T;.
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.88
D;D;D;D
M_CAP
Benign
0.020
T
MetaRNN
Pathogenic
0.86
D;D;D;D
MetaSVM
Benign
-0.67
T
MutationAssessor
Uncertain
2.6
.;M;.;.
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-4.0
D;D;D;D
REVEL
Uncertain
0.43
Sift
Uncertain
0.0020
D;D;D;D
Sift4G
Uncertain
0.021
D;D;D;D
Polyphen
0.99
D;D;.;D
Vest4
0.69
MutPred
0.77
.;Gain of methylation at M960 (P = 0.0209);.;.;
MVP
0.55
MPC
0.54
ClinPred
0.98
D
GERP RS
4.7
Varity_R
0.85
gMVP
0.73

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: chr4-533085; API