rs34859055

Variant names:

• chr8-18071253-T-TACA
• rs34859055
• NM_177924.5:c.216+46_216+47insTGT

Your query was ambiguous. Multiple possible variants found:

• chr8-18071253-T-TACA
• chr8-18071253-T-TATA
• chr8-18071253-T-TATC

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+47insTGT 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: not found (cov: 0)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: ASAH1 NM_177924.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469
• Publications: 0 publications found

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

ACMG classification

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	c.216+46_216+47insTGT		intron_variant	Intron 3 of 13	ENST00000637790.2	NP_808592.2

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000116 AC: 1 AN: 863340 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 431872

African (AFR) AF: 0.0000530 AC: 1 AN: 18870

American (AMR) AF: 0.00 AC: 0 AN: 13800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15414

East Asian (EAS) AF: 0.00 AC: 0 AN: 26906

South Asian (SAS) AF: 0.00 AC: 0 AN: 32774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2508

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 689450

Other (OTH) AF: 0.00 AC: 0 AN: 35334

GnomAD4 genome Cov.: 0

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

Other links and lift over

dbSNP: rs34859055; hg19: chr8-17928762;