rs3740767

chr11-76990562-G-Achr11-76990562-G-Cchr11-76990562-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018367.7(ACER3):c.426G>A(p.Pro142=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 1,464,408 control chromosomes in the GnomAD database, including 383,244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (30763 hom., cov: 33)
  • Exomes 𝑓: 0.72 (352481 hom.)
• Consequence: ACER3 NM_018367.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.117

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]

LOC124902721 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 11-76990562-G-A is Benign according to our data. Variant chr11-76990562-G-A is described in ClinVar as [Benign]. Clinvar id is 1164299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.117 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACER3	NM_018367.7	c.426G>A	p.Pro142=	synonymous_variant	6/11	ENST00000532485.6
LOC124902721	XR_007062792.1	n.118-31549C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACER3	ENST00000532485.6	c.426G>A	p.Pro142=	synonymous_variant	6/11	1	NM_018367.7	P1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90763 AN: 151988 Hom.: 30760 Cov.: 33

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.611

GnomAD3 exomes AF: 0.679 AC: 169281 AN: 249282 Hom.: 60385 AF XY: 0.694 AC XY: 93653 AN XY: 134850

Gnomad AFR exome AF: 0.251

Gnomad AMR exome AF: 0.502

Gnomad ASJ exome AF: 0.764

Gnomad EAS exome AF: 0.670

Gnomad SAS exome AF: 0.701

Gnomad FIN exome AF: 0.771

Gnomad NFE exome AF: 0.762

Gnomad OTH exome AF: 0.707

GnomAD4 exome AF: 0.724 AC: 950507 AN: 1312300 Hom.: 352481 Cov.: 26 AF XY: 0.727 AC XY: 476902 AN XY: 656282

Gnomad4 AFR exome AF: 0.221

Gnomad4 AMR exome AF: 0.504

Gnomad4 ASJ exome AF: 0.761

Gnomad4 EAS exome AF: 0.677

Gnomad4 SAS exome AF: 0.696

Gnomad4 FIN exome AF: 0.770

Gnomad4 NFE exome AF: 0.753

Gnomad4 OTH exome AF: 0.694

GnomAD4 genome AF: 0.597 AC: 90785 AN: 152108 Hom.: 30763 Cov.: 33 AF XY: 0.596 AC XY: 44326 AN XY: 74364

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.663

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.764

Gnomad4 OTH AF: 0.613

Alfa AF: 0.729 Hom.: 86411

Bravo AF: 0.567

Asia WGS AF: 0.625 AC: 2175 AN: 3478

EpiCase AF: 0.763

EpiControl AF: 0.763

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 11, 2020	- -

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). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	9.0
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs3740767; hg19: chr11-76701606;