NM_001253852.3:c.52_53delTG
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001253852.3(AP4B1):c.52_53delTG(p.Cys18GlnfsTer7) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,984 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
AP4B1
NM_001253852.3 frameshift
NM_001253852.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.90
Publications
1 publications found
Genes affected
AP4B1 (HGNC:572): (adaptor related protein complex 4 subunit beta 1) This gene encodes a subunit of a heterotetrameric adapter-like complex 4 that is involved in targeting proteins from the trans-Golgi network to the endosomal-lysosomal system. Mutations in this gene are associated with cerebral palsy spastic quadriplegic type 5 (CPSQ5) disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
DCLRE1B (HGNC:17641): (DNA cross-link repair 1B) DNA interstrand cross-links prevent strand separation, thereby physically blocking transcription, replication, and segregation of DNA. DCLRE1B is one of several evolutionarily conserved genes involved in repair of interstrand cross-links (Dronkert et al., 2000 [PubMed 10848582]).[supplied by OMIM, Mar 2008]
DCLRE1B Gene-Disease associations (from GenCC):
- dyskeratosis congenita, autosomal recessive 8Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 60 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-113904664-GCA-G is Pathogenic according to our data. Variant chr1-113904664-GCA-G is described in ClinVar as Pathogenic. ClinVar VariationId is 2971411.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001253852.3. 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 |
|---|---|---|---|---|---|---|---|---|---|
| AP4B1 | NM_001253852.3 | MANE Select | c.52_53delTG | p.Cys18GlnfsTer7 | frameshift | Exon 1 of 10 | NP_001240781.1 | Q9Y6B7-1 | |
| AP4B1 | NM_001438373.1 | c.52_53delTG | p.Cys18GlnfsTer7 | frameshift | Exon 2 of 11 | NP_001425302.1 | |||
| AP4B1 | NM_006594.5 | c.52_53delTG | p.Cys18GlnfsTer7 | frameshift | Exon 2 of 11 | NP_006585.2 | Q9Y6B7-1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| AP4B1 | ENST00000369569.6 | TSL:1 MANE Select | c.52_53delTG | p.Cys18GlnfsTer7 | frameshift | Exon 1 of 10 | ENSP00000358582.1 | Q9Y6B7-1 | |
| AP4B1 | ENST00000256658.8 | TSL:1 | c.52_53delTG | p.Cys18GlnfsTer7 | frameshift | Exon 2 of 11 | ENSP00000256658.4 | Q9Y6B7-1 | |
| AP4B1 | ENST00000863127.1 | c.52_53delTG | p.Cys18GlnfsTer7 | frameshift | Exon 1 of 11 | ENSP00000533186.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1460984Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726828 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1460984
Hom.:
AF XY:
AC XY:
1
AN XY:
726828
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33450
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
1
AN:
86210
European-Finnish (FIN)
AF:
AC:
0
AN:
53416
Middle Eastern (MID)
AF:
AC:
0
AN:
5056
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111988
Other (OTH)
AF:
AC:
0
AN:
60306
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
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2
0.00
0.20
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0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
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10
<30
30-35
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
1
-
-
Hereditary spastic paraplegia 47 (1)
1
-
-
not provided (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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