rs745563663

Variant summary

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

The ENST00000453061.7(PIGG):​c.2207C>A​(p.Ala736Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. A736V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PIGG
ENST00000453061.7 missense

Scores

1
10
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.68
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]

Genome browser will be placed here

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, 0.91

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PIGGNM_001127178.3 linkuse as main transcriptc.2207C>A p.Ala736Glu missense_variant 10/13 ENST00000453061.7 NP_001120650.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PIGGENST00000453061.7 linkuse as main transcriptc.2207C>A p.Ala736Glu missense_variant 10/131 NM_001127178.3 ENSP00000415203 P4Q5H8A4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248482
Hom.:
0
AF XY:
0.00000744
AC XY:
1
AN XY:
134382
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000291
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1460872
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
726676
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Uncertain
0.094
D
BayesDel_noAF
Uncertain
-0.020
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.10
.;T;T;.
Eigen
Benign
0.092
Eigen_PC
Benign
-0.015
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Benign
0.020
T
MetaRNN
Pathogenic
0.91
D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
.;M;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.50
T
PROVEAN
Uncertain
-3.0
D;D;D;D
REVEL
Benign
0.29
Sift
Uncertain
0.0060
D;D;D;D
Sift4G
Benign
0.37
T;T;T;T
Polyphen
1.0
D;D;.;D
Vest4
0.85
MutPred
0.70
.;Gain of sheet (P = 0.0827);.;.;
MVP
0.24
MPC
0.74
ClinPred
0.94
D
GERP RS
3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.41
gMVP
0.86

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: rs745563663; hg19: chr4-520965; API