NM_018367.7:c.426G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.117

Publications

27 publications found

Variant links:

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 links:

ACER3-AS1 (HGNC:58067):

ACER3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACER3	NM_018367.7 link	c.426G>A	p.Pro142Pro	synonymous_variant	Exon 6 of 11	ENST00000532485.6	NP_060837.3	Q9NUN7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACER3	ENST00000532485.6 link	c.426G>A	p.Pro142Pro	synonymous_variant	Exon 6 of 11	1	NM_018367.7	ENSP00000434480.1		Q9NUN7-1

Frequencies

GnomAD3 genomes

AF:

0.597

AC:

90763

AN:

151988

Hom.:

30760

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.727

AC XY:

476902

AN XY:

656282

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.422

Heterozygous variant carriers

10641

21282

31924

42565

53206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17152

34304

51456

68608

85760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.597

AC:

90785

AN:

152108

Hom.:

30763

Cov.:

AF XY:

0.596

AC XY:

44326

AN XY:

74364

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1555

3109

4664

6218

7773

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

738

1476

2214

2952

3690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 11, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ACER3-related disorder

Benign:1

Oct 16, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

DANN

Benign

0.72

PhyloP100

0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over