chr10-50243242-C-T

Variant names:

• chr10-50243242-C-T
• rs1238593835
• NM_019893.4:c.470G>A

Variant summary

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

The NM_019893.4(ASAH2):​c.470G>A​(p.Ser157Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,918 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: ASAH2 NM_019893.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.24
• Publications: 0 publications found

Genes affected

ASAH2 (HGNC:18860): (N-acylsphingosine amidohydrolase 2) Ceramidases (EC 3.5.1.23), such as ASAH2, catalyze hydrolysis of the N-acyl linkage of ceramide, a second messenger in a variety of cellular events, to produce sphingosine. Sphingosine exerts both mitogenic and apoptosis-inducing activities, and its phosphorylated form functions as an intra- and intercellular second messenger (see MIM 603730) (Mitsutake et al., 2001 [PubMed 11328816]).[supplied by OMIM, Mar 2008]

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_019893.4. 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
	ASAH2	NM_019893.4	MANE Select	c.470G>A	p.Ser157Asn	missense	Exon 4 of 21	NP_063946.2	Q9NR71-1
	ASAH2	NM_001143974.3		c.470G>A	p.Ser157Asn	missense	Exon 4 of 20	NP_001137446.1	Q9NR71-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASAH2	ENST00000682911.1	MANE Select	c.470G>A	p.Ser157Asn	missense	Exon 4 of 21	ENSP00000506746.1	Q9NR71-1
	ASAH2	ENST00000395526.9	TSL:1	c.470G>A	p.Ser157Asn	missense	Exon 5 of 22	ENSP00000378897.3	Q9NR71-1
	ASAH2	ENST00000329428.11	TSL:1	c.470G>A	p.Ser157Asn	missense	Exon 3 of 19	ENSP00000329886.7

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461764 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727188

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111896

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152154 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74322

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.2
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.19
Sift	Benign	0.37	T
Sift4G	Uncertain	0.054	T
Polyphen		0.62	P
Vest4		0.45
MutPred		0.72		Gain of MoRF binding (P = 0.1926)
MVP		0.57
MPC		0.16
ClinPred		0.90	D
GERP RS		5.8
Varity_R		0.47
gMVP		0.65
Mutation Taster		=56/44	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

Other links and lift over

dbSNP: rs1238593835; hg19: chr10-52003002;