rs3740767

Variant names:

• chr11-76990562-G-A
• rs3740767
• NM_018367.7:c.426G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-76990562-G-A
• chr11-76990562-G-C
• chr11-76990562-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018367.7(ACER3):​c.426G>A​(p.Pro142Pro) 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:4
• Conservation: PhyloP100: 0.117
• Publications: 27 publications found

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]

ACER3 Gene-Disease associations (from GenCC):

• alkaline ceramidase 3 deficiency

  Inheritance: Unknown, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACER3-AS1 (HGNC:58067):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018367.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACER3	NM_018367.7	MANE Select	c.426G>A	p.Pro142Pro	synonymous	Exon 6 of 11	NP_060837.3
	ACER3	NM_001300953.2		c.315G>A	p.Pro105Pro	synonymous	Exon 5 of 10	NP_001287882.1	B7Z2Q2
	ACER3	NM_001300954.2		c.141G>A	p.Pro47Pro	synonymous	Exon 6 of 11	NP_001287883.1	B7Z2V2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACER3	ENST00000532485.6	TSL:1 MANE Select	c.426G>A	p.Pro142Pro	synonymous	Exon 6 of 11	ENSP00000434480.1	Q9NUN7-1
	ACER3	ENST00000278544.9	TSL:1	n.*266G>A		non_coding_transcript_exon	Exon 6 of 11	ENSP00000278544.5	J3KN85
	ACER3	ENST00000525194.5	TSL:1	n.*378G>A		non_coding_transcript_exon	Exon 7 of 11	ENSP00000432109.1	E9PKR3

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

GnomAD2 exomes AF: 0.679 AC: 169281 AN: 249282 AF XY: 0.694

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 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

African (AFR) AF: 0.221 AC: 7069 AN: 32024

American (AMR) AF: 0.504 AC: 21638 AN: 42960

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 18649 AN: 24520

East Asian (EAS) AF: 0.677 AC: 25946 AN: 38324

South Asian (SAS) AF: 0.696 AC: 57893 AN: 83164

European-Finnish (FIN) AF: 0.770 AC: 39082 AN: 50762

Middle Eastern (MID) AF: 0.676 AC: 3654 AN: 5402

European-Non Finnish (NFE) AF: 0.753 AC: 738414 AN: 980142

Other (OTH) AF: 0.694 AC: 38162 AN: 55002

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

African (AFR) AF: 0.258 AC: 10694 AN: 41464

American (AMR) AF: 0.545 AC: 8325 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2648 AN: 3470

East Asian (EAS) AF: 0.663 AC: 3434 AN: 5176

South Asian (SAS) AF: 0.686 AC: 3307 AN: 4822

European-Finnish (FIN) AF: 0.778 AC: 8225 AN: 10578

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.764 AC: 51979 AN: 68002

Other (OTH) AF: 0.613 AC: 1294 AN: 2110

Alfa AF: 0.702 Hom.: 116952

Bravo AF: 0.567

Asia WGS AF: 0.625 AC: 2175 AN: 3478

EpiCase AF: 0.763

EpiControl AF: 0.763

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	ACER3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.0
DANN	Benign	0.72
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3740767; hg19: chr11-76701606; COSMIC: COSV108076249;