rs1554988032

Variant names:

• chr11-76861074-A-C
• NM_018367.7:c.98A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-76861074-A-C
• chr11-76861074-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1 PM2 PP3_Strong

The NM_018367.7(ACER3):​c.98A>C​(p.Glu33Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000719 in 1,391,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ACER3 NM_018367.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.98

Genes affected

ACER3 (HGNC:16066): (alkaline ceramidase 3) Enables N-acylsphingosine amidohydrolase activity and metal ion binding activity. Involved in several processes, including myelination; positive regulation of cell population proliferation; and sphingolipid metabolic process. Is integral component of Golgi membrane and integral component of endoplasmic reticulum membrane. Biomarker of hepatocellular carcinoma and non-alcoholic steatohepatitis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity ACER3_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.987

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACER3	NM_018367.7	c.98A>C	p.Glu33Ala	missense_variant	Exon 1 of 11	ENST00000532485.6	NP_060837.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACER3	ENST00000532485.6	c.98A>C	p.Glu33Ala	missense_variant	Exon 1 of 11	1	NM_018367.7	ENSP00000434480.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1391032 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 686246

Gnomad4 AFR exome AF: 0.0000321

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D;D
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.91	D;T
M_CAP	Pathogenic	0.91	D
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Uncertain	0.54	D
MutationAssessor	Pathogenic	3.7	H;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.5	D;D
REVEL	Pathogenic	0.84
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	D;P
Vest4		0.65
MutPred		0.92		Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP		0.80
MPC		1.7
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.98
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-76572118;