NM_001346754.2:c.126C>T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001346754.2(PIGW):c.126C>T(p.Phe42Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PIGW
NM_001346754.2 synonymous
NM_001346754.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.787
Publications
0 publications found
Genes affected
PIGW (HGNC:23213): (phosphatidylinositol glycan anchor biosynthesis class W) The protein encoded by this gene is an inositol acyltransferase that acylates the inositol ring of phosphatidylinositol. This occurs in the endoplasmic reticulum and is a step in the biosynthesis of glycosylphosphatidylinositol (GPI), which anchors many cell surface proteins to the membrane. Defects in this gene are a cause of the age-dependent epileptic encephalopathy West syndrome as well as a syndrome exhibiting hyperphosphatasia and cognitive disability (HPMRS5). [provided by RefSeq, Jul 2017]
MYO19 (HGNC:26234): (myosin XIX) Enables actin binding activity. Involved in regulation of cytokinesis and regulation of mitochondrial fission. Acts upstream of or within mitochondrion migration along actin filament. Located in cytosol and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
Variant 17-36537227-C-T is Benign according to our data. Variant chr17-36537227-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3683855.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.787 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001346754.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PIGW | NM_001346754.2 | MANE Select | c.126C>T | p.Phe42Phe | synonymous | Exon 2 of 2 | NP_001333683.1 | Q7Z7B1 | |
| PIGW | NM_001346755.2 | c.126C>T | p.Phe42Phe | synonymous | Exon 2 of 2 | NP_001333684.1 | Q7Z7B1 | ||
| PIGW | NM_178517.5 | c.126C>T | p.Phe42Phe | synonymous | Exon 2 of 2 | NP_848612.2 | Q7Z7B1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PIGW | ENST00000614443.2 | TSL:1 MANE Select | c.126C>T | p.Phe42Phe | synonymous | Exon 2 of 2 | ENSP00000482202.1 | Q7Z7B1 | |
| PIGW | ENST00000619326.1 | TSL:1 | c.126C>T | p.Phe42Phe | synonymous | Exon 2 of 2 | ENSP00000480475.1 | A0A087WWS9 | |
| PIGW | ENST00000620233.1 | TSL:2 | c.126C>T | p.Phe42Phe | synonymous | Exon 2 of 2 | ENSP00000480021.1 | Q7Z7B1 |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 152178Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
0
AN:
152178
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461868Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727234 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1461868
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
727234
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33480
American (AMR)
AF:
AC:
1
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111990
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
1
1
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2
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0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome 0.00 AC: 0AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74338
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
152178
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74338
African (AFR)
AF:
AC:
0
AN:
41442
American (AMR)
AF:
AC:
0
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5198
South Asian (SAS)
AF:
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68032
Other (OTH)
AF:
AC:
0
AN:
2094
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
Hyperphosphatasia with intellectual disability syndrome 5 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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