22-29331890-AG-A
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001127.4(AP1B1):c.2335delC(p.Leu779SerfsTer26) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
AP1B1
NM_001127.4 frameshift
NM_001127.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.15
Publications
0 publications found
Genes affected
AP1B1 (HGNC:554): (adaptor related protein complex 1 subunit beta 1) Adaptor protein complex 1 is found at the cytoplasmic face of coated vesicles located at the Golgi complex, where it mediates both the recruitment of clathrin to the membrane and the recognition of sorting signals within the cytosolic tails of transmembrane receptors. This complex is a heterotetramer composed of two large, one medium, and one small adaptin subunit. The protein encoded by this gene serves as one of the large subunits of this complex and is a member of the adaptin protein family. This gene is a candidate meningioma gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
AP1B1 Gene-Disease associations (from GenCC):
- ichthyosiform erythroderma, corneal involvement, and hearing lossInheritance: AR Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, G2P, ClinGen
- MEDNIK syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 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 22-29331890-AG-A is Pathogenic according to our data. Variant chr22-29331890-AG-A is described in ClinVar as Pathogenic. ClinVar VariationId is 805797.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001127.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| AP1B1 | MANE Select | c.2335delC | p.Leu779SerfsTer26 | frameshift | Exon 18 of 23 | NP_001118.3 | |||
| AP1B1 | c.2335delC | p.Leu779SerfsTer26 | frameshift | Exon 18 of 22 | NP_001365491.1 | ||||
| AP1B1 | c.2314delC | p.Leu772SerfsTer26 | frameshift | Exon 17 of 22 | NP_001365492.1 | Q10567-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| AP1B1 | TSL:1 MANE Select | c.2335delC | p.Leu779SerfsTer26 | frameshift | Exon 18 of 23 | ENSP00000350199.2 | Q10567-1 | ||
| AP1B1 | TSL:1 | c.2254delC | p.Leu752SerfsTer26 | frameshift | Exon 17 of 21 | ENSP00000319361.7 | Q10567-4 | ||
| AP1B1 | TSL:1 | n.431delC | non_coding_transcript_exon | Exon 1 of 4 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1458362Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 725384
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1458362
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
725384
African (AFR)
AF:
AC:
0
AN:
33410
American (AMR)
AF:
AC:
0
AN:
44652
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26036
East Asian (EAS)
AF:
AC:
0
AN:
39520
South Asian (SAS)
AF:
AC:
0
AN:
86204
European-Finnish (FIN)
AF:
AC:
0
AN:
52734
Middle Eastern (MID)
AF:
AC:
0
AN:
5752
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1109816
Other (OTH)
AF:
AC:
0
AN:
60238
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Autosomal recessive keratitis-ichthyosis-deafness syndrome (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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