NM_001127178.3:c.901+10T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001127178.3(PIGG):​c.901+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,452,702 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: not found (cov: 33)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

PIGG
NM_001127178.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.231

Publications

0 publications found
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]
PIGG Gene-Disease associations (from GenCC):
  • intellectual disability, autosomal recessive 53
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PIGGNM_001127178.3 linkc.901+10T>C intron_variant Intron 5 of 12 ENST00000453061.7 NP_001120650.1 Q5H8A4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PIGGENST00000453061.7 linkc.901+10T>C intron_variant Intron 5 of 12 1 NM_001127178.3 ENSP00000415203.2 Q5H8A4-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.0000122
AC:
3
AN:
246844
AF XY:
0.0000150
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000898
Gnomad ASJ exome
AF:
0.00
Gnomad EAS 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:
0.00000275
AC:
4
AN:
1452702
Hom.:
0
Cov.:
28
AF XY:
0.00000415
AC XY:
3
AN XY:
722162
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33194
American (AMR)
AF:
0.0000914
AC:
4
AN:
43772
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25918
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39600
South Asian (SAS)
AF:
0.00
AC:
0
AN:
84946
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53340
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5742
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1106098
Other (OTH)
AF:
0.00
AC:
0
AN:
60092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
0.28
DANN
Benign
0.52
PhyloP100
-0.23
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs782012518; hg19: chr4-502769; API