chr9-19409181-T-C

Position:

• chr9-19409181-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001010887.3(ACER2):​c.97T>C​(p.Phe33Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000277 in 1,443,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: ACER2 NM_001010887.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.75

Genes affected

ACER2 (HGNC:23675): (alkaline ceramidase 2) The sphingolipid metabolite sphingosine-1-phosphate promotes cell proliferation and survival, whereas its precursor, sphingosine, has the opposite effect. The ceramidase ACER2 hydrolyzes very long chain ceramides to generate sphingosine (Xu et al., 2006 [PubMed 16940153]).[supplied by OMIM, Jul 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.876

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACER2	NM_001010887.3	c.97T>C	p.Phe33Leu	missense_variant	1/6	ENST00000340967.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACER2	ENST00000340967.3	c.97T>C	p.Phe33Leu	missense_variant	1/6	1	NM_001010887.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1443778 Hom.: 0 Cov.: 31 AF XY: 0.00000558 AC XY: 4 AN XY: 716318

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000361

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.06e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.36	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.73		Gain of glycosylation at S38 (P = 0.1897);
MVP		0.72
MPC		0.52
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.88
gMVP		0.97

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

LitVar

Other links and lift over

dbSNP: rs1830007618; hg19: chr9-19409179;