NM_001010887.3:c.25C>A

Variant names:

• chr9-19409109-C-A
• rs10122075
• NM_001010887.3:c.25C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010887.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACER2	NM_001010887.3	MANE Select	c.25C>A	p.Gln9Lys	missense	Exon 1 of 6	NP_001010887.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACER2	ENST00000340967.3	TSL:1 MANE Select	c.25C>A	p.Gln9Lys	missense	Exon 1 of 6	ENSP00000342609.2

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

GnomAD2 exomes AF: 0.00112 AC: 254 AN: 225856 AF XY: 0.000898

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 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

African (AFR) AF: 0.0192 AC: 639 AN: 33284

American (AMR) AF: 0.000650 AC: 28 AN: 43064

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25786

East Asian (EAS) AF: 0.00 AC: 0 AN: 39220

South Asian (SAS) AF: 0.00 AC: 0 AN: 83854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52072

Middle Eastern (MID) AF: 0.000540 AC: 3 AN: 5558

European-Non Finnish (NFE) AF: 0.0000145 AC: 16 AN: 1106966

Other (OTH) AF: 0.00117 AC: 70 AN: 59870

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

African (AFR) AF: 0.0176 AC: 731 AN: 41574

American (AMR) AF: 0.00131 AC: 20 AN: 15310

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00295 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 v4.9

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
PhyloP100		5.7
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
PromoterAI		0.12	Neutral
Varity_R		0.30
gMVP		0.89
Mutation Taster		=238/62	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: rs10122075; hg19: chr9-19409107;