GeneBe

8-18084285-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004315.6(ASAH1):​c.126+391T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ASAH1
NM_004315.6 intron

Scores

7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.345

Publications

3 publications found
Variant links:
Genes affected
ASAH1 (HGNC:735): (N-acylsphingosine amidohydrolase 1) This gene encodes a member of the acid ceramidase family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. Processing of this preproprotein generates alpha and beta subunits that heterodimerize to form the mature lysosomal enzyme, which catalyzes the degradation of ceramide into sphingosine and free fatty acid. This enzyme is overexpressed in multiple human cancers and may play a role in cancer progression. Mutations in this gene are associated with the lysosomal storage disorder, Farber lipogranulomatosis, and a neuromuscular disorder, spinal muscular atrophy with progressive myoclonic epilepsy. [provided by RefSeq, Oct 2015]
ASAH1-AS1 (HGNC:55603): (ASAH1 antisense RNA 1)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08791667).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004315.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ASAH1
NM_004315.6
c.126+391T>C
intron
N/ANP_004306.3
ASAH1
NM_001127505.3
c.126+391T>C
intron
N/ANP_001120977.1Q13510-3
ASAH1
NM_177924.5
MANE Select
c.-227T>C
upstream_gene
N/ANP_808592.2Q13510-1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ASAH1
ENST00000381733.9
TSL:1
c.126+391T>C
intron
N/AENSP00000371152.4Q13510-2
ASAH1
ENST00000314146.10
TSL:1
c.126+391T>C
intron
N/AENSP00000326970.10Q13510-3
ASAH1
ENST00000637244.1
TSL:1
n.*292T>C
non_coding_transcript_exon
Exon 1 of 14ENSP00000490188.1A0A1B0GUP1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1284800
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
624166
African (AFR)
AF:
0.00
AC:
0
AN:
28174
American (AMR)
AF:
0.00
AC:
0
AN:
20056
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
18862
East Asian (EAS)
AF:
0.00
AC:
0
AN:
34728
South Asian (SAS)
AF:
0.00
AC:
0
AN:
62782
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
29538
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3604
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1033704
Other (OTH)
AF:
0.00
AC:
0
AN:
53352
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.31
BayesDel_noAF
Benign
-0.73
CADD
Benign
1.9
DANN
Benign
0.51
DEOGEN2
Benign
0.021
T
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.15
T
MetaRNN
Benign
0.088
T
PhyloP100
-0.34
GERP RS
2.4
PromoterAI
0.15
Neutral
Mutation Taster
=300/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs34466559; hg19: chr8-17941794; API