rs10122075

chr9-19409109-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001010887.3(ACER2):c.25C>A(p.Gln9Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000943 in 1,601,998 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0049 (8 hom., cov: 33)
  • Exomes 𝑓: 0.00052 (5 hom.)
• Consequence: ACER2 NM_001010887.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.69

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008359581).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00495 (754/152324) while in subpopulation AFR AF= 0.0176 (731/41574). AF 95% confidence interval is 0.0165. There are 8 homozygotes in gnomad4. There are 361 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACER2	NM_001010887.3	c.25C>A	p.Gln9Lys	missense_variant	1/6	ENST00000340967.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACER2	ENST00000340967.3	c.25C>A	p.Gln9Lys	missense_variant	1/6	1	NM_001010887.3	P1

Frequencies

GnomAD3 genomes AF: 0.00495 AC: 753 AN: 152206 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

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: 0.00143

GnomAD3 exomes AF: 0.00112 AC: 254 AN: 225856 Hom.: 2 AF XY: 0.000898 AC XY: 110 AN XY: 122540

Gnomad AFR exome AF: 0.0173

Gnomad AMR exome AF: 0.000525

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000396

Gnomad OTH exome AF: 0.000180

GnomAD4 exome AF: 0.000521 AC: 756 AN: 1449674 Hom.: 5 Cov.: 31 AF XY: 0.000432 AC XY: 311 AN XY: 719858

Gnomad4 AFR exome AF: 0.0192

Gnomad4 AMR exome AF: 0.000650

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000145

Gnomad4 OTH exome AF: 0.00117

GnomAD4 genome AF: 0.00495 AC: 754 AN: 152324 Hom.: 8 Cov.: 33 AF XY: 0.00485 AC XY: 361 AN XY: 74486

Gnomad4 AFR AF: 0.0176

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00301 Hom.: 3

Bravo AF: 0.00595

ESP6500AA AF: 0.0164 AC: 72

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.00145 AC: 175

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.34
Cadd	Uncertain	23
Dann	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.037
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0084	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.10
Sift	Benign	0.54	T
Sift4G	Benign	0.89	T
Polyphen		0.038	B
Vest4		0.50
MVP		0.42
MPC		0.14
ClinPred		0.097	T
GERP RS		5.0
Varity_R		0.30
gMVP		0.89

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: rs10122075; hg19: chr9-19409107;