1-40092462-AT-A
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000310.4(PPT1):c.169delA(p.Met57TrpfsTer14) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,622 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
PPT1
NM_000310.4 frameshift
NM_000310.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.91
Publications
0 publications found
Genes affected
PPT1 (HGNC:9325): (palmitoyl-protein thioesterase 1) The protein encoded by this gene is a small glycoprotein involved in the catabolism of lipid-modified proteins during lysosomal degradation. The encoded enzyme removes thioester-linked fatty acyl groups such as palmitate from cysteine residues. Defects in this gene are a cause of infantile neuronal ceroid lipofuscinosis 1 (CLN1, or INCL) and neuronal ceroid lipofuscinosis 4 (CLN4). Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Dec 2008]
PPT1 Gene-Disease associations (from GenCC):
- neuronal ceroid lipofuscinosisInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- neuronal ceroid lipofuscinosis 1Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet, Myriad Women’s Health
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-40092462-AT-A is Pathogenic according to our data. Variant chr1-40092462-AT-A is described in ClinVar as Pathogenic. ClinVar VariationId is 2752503.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000310.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PPT1 | NM_000310.4 | MANE Select | c.169delA | p.Met57TrpfsTer14 | frameshift | Exon 2 of 9 | NP_000301.1 | ||
| PPT1 | NM_001363695.2 | c.169delA | p.Met57TrpfsTer14 | frameshift | Exon 2 of 8 | NP_001350624.1 | |||
| PPT1 | NM_001142604.2 | c.125-2951delA | intron | N/A | NP_001136076.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PPT1 | ENST00000642050.2 | MANE Select | c.169delA | p.Met57TrpfsTer14 | frameshift | Exon 2 of 9 | ENSP00000493153.1 | ||
| PPT1 | ENST00000433473.8 | TSL:1 | c.166delA | p.Met56TrpfsTer14 | frameshift | Exon 2 of 9 | ENSP00000394863.4 | ||
| PPT1 | ENST00000530704.6 | TSL:1 | n.169delA | non_coding_transcript_exon | Exon 2 of 9 | ENSP00000431655.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461622Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727126 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461622
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
727126
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33472
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
0
AN:
39692
South Asian (SAS)
AF:
AC:
0
AN:
86252
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111776
Other (OTH)
AF:
AC:
1
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
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1
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Neuronal ceroid lipofuscinosis 1 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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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