8-18056822-ACTTC-ACTTCCTTC

Variant names:

• chr8-18056822-A-ACTTC
• rs35838806
• NM_177924.5:c.*708_*711dupGAAG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_177924.5(ASAH1):​c.*708_*711dupGAAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: ASAH1 NM_177924.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.659
• Publications: 2 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: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• spinal muscular atrophy-progressive myoclonic epilepsy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177924.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASAH1	NM_177924.5	MANE Select	c.*708_*711dupGAAG		3_prime_UTR	Exon 14 of 14	NP_808592.2	Q13510-1
	ASAH1	NM_004315.6		c.*708_*711dupGAAG		3_prime_UTR	Exon 14 of 14	NP_004306.3
	ASAH1	NM_001127505.3		c.*708_*711dupGAAG		3_prime_UTR	Exon 14 of 14	NP_001120977.1	Q13510-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASAH1	ENST00000637790.2	TSL:1 MANE Select	c.*708_*711dupGAAG		3_prime_UTR	Exon 14 of 14	ENSP00000490272.1	Q13510-1
	ASAH1	ENST00000381733.9	TSL:1	c.*708_*711dupGAAG		3_prime_UTR	Exon 14 of 14	ENSP00000371152.4	Q13510-2
	ASAH1	ENST00000637244.1	TSL:1	n.*2414_*2417dupGAAG		non_coding_transcript_exon	Exon 14 of 14	ENSP00000490188.1	A0A1B0GUP1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.66

Splicing

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

Other links and lift over

dbSNP: rs35838806; hg19: chr8-17914331;