15-67204086-C-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_024666.5(AAGAB):c.778G>T(p.Glu260Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
AAGAB
NM_024666.5 stop_gained
NM_024666.5 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 7.13
Genes affected
AAGAB (HGNC:25662): (alpha and gamma adaptin binding protein) The protein encoded by this gene interacts with the gamma-adaptin and alpha-adaptin subunits of complexes involved in clathrin-coated vesicle trafficking. Mutations in this gene are associated with type I punctate palmoplantar keratoderma. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 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 15-67204086-C-A is Pathogenic according to our data. Variant chr15-67204086-C-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2431961.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AAGAB | NM_024666.5 | c.778G>T | p.Glu260Ter | stop_gained | 8/10 | ENST00000261880.10 | |
AAGAB | NM_001271885.2 | c.451G>T | p.Glu151Ter | stop_gained | 8/10 | ||
AAGAB | NM_001271886.2 | c.451G>T | p.Glu151Ter | stop_gained | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AAGAB | ENST00000261880.10 | c.778G>T | p.Glu260Ter | stop_gained | 8/10 | 1 | NM_024666.5 | P1 | |
AAGAB | ENST00000542650.5 | c.451G>T | p.Glu151Ter | stop_gained | 8/10 | 2 | |||
AAGAB | ENST00000561452.5 | c.451G>T | p.Glu151Ter | stop_gained | 8/10 | 5 | |||
AAGAB | ENST00000538028.1 | n.459G>T | non_coding_transcript_exon_variant | 5/7 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Palmoplantar keratoderma, punctate type 1A Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jan 26, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -42
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.