Genetic Variant ASAH1:c.216+46_216+47insGAT (chr8-18071253-T-TATC) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_177924.5(ASAH1):c.216+46_216+47insGAT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

ASAH1
NM_177924.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.469

Publications

1 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 Gene-Disease associations (from GenCC):

ASAH1-related sphingolipidosis
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Farber lipogranulomatosis
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
spinal muscular atrophy-progressive myoclonic epilepsy syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P

ASAH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASAH1	NM_177924.5 link	c.216+46_216+47insGAT		intron_variant	Intron 3 of 13	ENST00000637790.2	NP_808592.2	Q13510-1Q53H01A8K0B6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASAH1	ENST00000637790.2 link	c.216+46_216+47insGAT		intron_variant	Intron 3 of 13	1	NM_177924.5	ENSP00000490272.1		Q13510-1

Frequencies

GnomAD3 genomes

AF:

0.00000678

AC:

AN:

147496

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000116

AC:

AN:

863340

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

431872

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18870

American (AMR)

AF:

0.00

AC:

AN:

13800

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15414

East Asian (EAS)

AF:

0.00

AC:

AN:

26906

South Asian (SAS)

AF:

0.00

AC:

AN:

32774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2508

European-Non Finnish (NFE)

AF:

0.00000145

AC:

AN:

689450

Other (OTH)

AF:

0.00

AC:

AN:

35334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000678

AC:

AN:

147496

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71886

show subpopulations

African (AFR)

AF:

0.0000249

AC:

AN:

40118

American (AMR)

AF:

0.00

AC:

AN:

14954

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3428

East Asian (EAS)

AF:

0.00

AC:

AN:

5062

South Asian (SAS)

AF:

0.00

AC:

AN:

4720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66398

Other (OTH)

AF:

0.00

AC:

AN:

2018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.47

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over