4-523897-G-C

Position:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001127178.3(PIGG):ā€‹c.2053G>Cā€‹(p.Gly685Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000849 in 1,530,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000058 ( 0 hom. )

Consequence

PIGG
NM_001127178.3 missense

Scores

3
8
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.46
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33234492).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PIGGNM_001127178.3 linkc.2053G>C p.Gly685Arg missense_variant 9/13 ENST00000453061.7 NP_001120650.1 Q5H8A4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PIGGENST00000453061.7 linkc.2053G>C p.Gly685Arg missense_variant 9/131 NM_001127178.3 ENSP00000415203.2 Q5H8A4-1

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152228
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000140
AC:
2
AN:
143012
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
76470
show subpopulations
Gnomad AFR exome
AF:
0.000130
Gnomad AMR exome
AF:
0.0000419
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:
0.00000580
AC:
8
AN:
1378318
Hom.:
0
Cov.:
32
AF XY:
0.00000296
AC XY:
2
AN XY:
675620
show subpopulations
Gnomad4 AFR exome
AF:
0.000223
Gnomad4 AMR exome
AF:
0.0000284
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152228
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000491
ExAC
AF:
0.0000182
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.67
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.20
CADD
Benign
23
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.080
.;T;T;.
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.92
D;D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.33
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
.;M;.;.
PrimateAI
Uncertain
0.62
T
PROVEAN
Pathogenic
-5.0
D;D;D;D
REVEL
Benign
0.19
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Uncertain
0.0070
D;D;D;D
Polyphen
0.99
D;D;.;D
Vest4
0.56
MVP
0.44
MPC
0.70
ClinPred
0.96
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.61
gMVP
0.79

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: rs200770933; hg19: chr4-517686; API