ENST00000260648.10:c.237_240delACAA
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The ENST00000260648.10(PREPL):c.237_240delACAA(p.Gln80LysfsTer16) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,600 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: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
PREPL
ENST00000260648.10 frameshift
ENST00000260648.10 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.56
Publications
0 publications found
Genes affected
PREPL (HGNC:30228): (prolyl endopeptidase like) The protein encoded by this gene belongs to the prolyl oligopeptidase subfamily of serine peptidases. Mutations in this gene have been associated with hypotonia-cystinuria syndrome, also known as the 2p21 deletion syndrome. Several alternatively spliced transcript variants encoding either the same or different isoforms have been described for this gene.[provided by RefSeq, Jan 2010]
PREPL Gene-Disease associations (from GenCC):
- hypotonia-cystinuria syndromeInheritance: AR Classification: STRONG Submitted by: G2P
- myasthenic syndrome, congenital, 22Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
new If you want to explore the variant's impact on the transcript ENST00000260648.10, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.
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 2-44346369-CTTGT-C is Pathogenic according to our data. Variant chr2-44346369-CTTGT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 478314.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: ENST00000260648.10. 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 |
|---|---|---|---|---|---|---|---|---|---|
| PREPL | MANE Select | c.-31_-28delACAA | 5_prime_UTR | Exon 2 of 14 | NP_001165084.1 | Q4J6C6-4 | |||
| PREPL | c.237_240delACAA | p.Gln80LysfsTer16 | frameshift | Exon 3 of 15 | NP_001165074.1 | Q4J6C6-1 | |||
| PREPL | c.237_240delACAA | p.Gln80LysfsTer16 | frameshift | Exon 3 of 15 | NP_001165077.1 | Q4J6C6-1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PREPL | TSL:1 | c.237_240delACAA | p.Gln80LysfsTer16 | frameshift | Exon 2 of 14 | ENSP00000260648.6 | Q4J6C6-1 | ||
| PREPL | TSL:1 | c.237_240delACAA | p.Gln80LysfsTer16 | frameshift | Exon 3 of 15 | ENSP00000386543.1 | Q4J6C6-1 | ||
| PREPL | TSL:1 | c.237_240delACAA | p.Gln80LysfsTer16 | frameshift | Exon 2 of 13 | ENSP00000367772.3 | Q4J6C6-3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460600Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726620 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2
AN:
1460600
Hom.:
AF XY:
AC XY:
1
AN XY:
726620
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33418
American (AMR)
AF:
AC:
0
AN:
44582
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26096
East Asian (EAS)
AF:
AC:
0
AN:
39550
South Asian (SAS)
AF:
AC:
1
AN:
86094
European-Finnish (FIN)
AF:
AC:
0
AN:
53266
Middle Eastern (MID)
AF:
AC:
0
AN:
5760
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111500
Other (OTH)
AF:
AC:
0
AN:
60334
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Myasthenic syndrome, congenital, 22 (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
MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.
Publications
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