11-76926636-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_018367.7(ACER3):c.183G>A(p.Lys61=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 1,590,284 control chromosomes in the GnomAD database, including 394,028 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (28063 hom., cov: 32)
  • Exomes 𝑓: 0.71 (365965 hom.)
• Consequence: ACER3 NM_018367.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.145

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 Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 11-76926636-G-A is Benign according to our data. Variant chr11-76926636-G-A is described in ClinVar as [Benign]. Clinvar id is 1164298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.145 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACER3	NM_018367.7	c.183G>A	p.Lys61=	synonymous_variant	2/11	ENST00000532485.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACER3	ENST00000532485.6	c.183G>A	p.Lys61=	synonymous_variant	2/11	1	NM_018367.7	P1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86912 AN: 151884 Hom.: 28061 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.583

GnomAD3 exomes AF: 0.641 AC: 159360 AN: 248682 Hom.: 54056 AF XY: 0.655 AC XY: 88123 AN XY: 134472

Gnomad AFR exome AF: 0.250

Gnomad AMR exome AF: 0.450

Gnomad ASJ exome AF: 0.729

Gnomad EAS exome AF: 0.629

Gnomad SAS exome AF: 0.636

Gnomad FIN exome AF: 0.710

Gnomad NFE exome AF: 0.735

Gnomad OTH exome AF: 0.666

GnomAD4 exome AF: 0.705 AC: 1014695 AN: 1438284 Hom.: 365965 Cov.: 35 AF XY: 0.706 AC XY: 505818 AN XY: 716272

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.457

Gnomad4 ASJ exome AF: 0.728

Gnomad4 EAS exome AF: 0.639

Gnomad4 SAS exome AF: 0.636

Gnomad4 FIN exome AF: 0.710

Gnomad4 NFE exome AF: 0.739

Gnomad4 OTH exome AF: 0.675

GnomAD4 genome AF: 0.572 AC: 86931 AN: 152000 Hom.: 28063 Cov.: 32 AF XY: 0.569 AC XY: 42244 AN XY: 74280

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.737

Gnomad4 OTH AF: 0.586

Alfa AF: 0.665 Hom.: 16232

Bravo AF: 0.547

Asia WGS AF: 0.561 AC: 1951 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

ACER3-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	6.2
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs4479014; hg19: chr11-76637680; COSMIC: COSV53603982;