rs387906335
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_016006.6(ABHD5):c.594dupC(p.Arg199GlnfsTer11) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
ABHD5
NM_016006.6 frameshift
NM_016006.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.40
Publications
5 publications found
Genes affected
ABHD5 (HGNC:21396): (abhydrolase domain containing 5, lysophosphatidic acid acyltransferase) The protein encoded by this gene belongs to a large family of proteins defined by an alpha/beta hydrolase fold, and contains three sequence motifs that correspond to a catalytic triad found in the esterase/lipase/thioesterase subfamily. It differs from other members of this subfamily in that its putative catalytic triad contains an asparagine instead of the serine residue. Mutations in this gene have been associated with Chanarin-Dorfman syndrome, a triglyceride storage disease with impaired long-chain fatty acid oxidation. [provided by RefSeq, Jul 2008]
ABHD5 Gene-Disease associations (from GenCC):
- Dorfman-Chanarin diseaseInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, 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 3-43711795-T-TC is Pathogenic according to our data. Variant chr3-43711795-T-TC is described in ClinVar as Pathogenic. ClinVar VariationId is 5352.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_016006.6. 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 |
|---|---|---|---|---|---|---|---|---|---|
| ABHD5 | NM_016006.6 | MANE Select | c.594dupC | p.Arg199GlnfsTer11 | frameshift | Exon 4 of 7 | NP_057090.2 | ||
| ABHD5 | NM_001355186.2 | c.594dupC | p.Arg199GlnfsTer11 | frameshift | Exon 4 of 8 | NP_001342115.1 | |||
| ABHD5 | NM_001365649.1 | c.471dupC | p.Arg158GlnfsTer11 | frameshift | Exon 4 of 7 | NP_001352578.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ABHD5 | ENST00000644371.2 | MANE Select | c.594dupC | p.Arg199GlnfsTer11 | frameshift | Exon 4 of 7 | ENSP00000495778.1 | ||
| ABHD5 | ENST00000458276.7 | TSL:1 | c.594dupC | p.Arg199GlnfsTer11 | frameshift | Exon 4 of 6 | ENSP00000390849.3 | ||
| ABHD5 | ENST00000454293.2 | TSL:3 | c.471dupC | p.Arg158GlnfsTer11 | frameshift | Exon 4 of 8 | ENSP00000412014.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461880Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727240 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461880
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727240
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1112004
Other (OTH)
AF:
AC:
1
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
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
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Triglyceride storage disease with ichthyosis (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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