Variant 11-76926636-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.145

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 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	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 linkuse as main transcript	c.183G>A	p.Lys61=	synonymous_variant	2/11	1	NM_018367.7	P1	Q9NUN7-1

Frequencies

GnomAD3 genomes

AF:

0.572

AC:

86912

AN:

151884

Hom.:

28061

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.706

AC XY:

505818

AN XY:

716272

show subpopulations

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.:

AF XY:

0.569

AC XY:

42244

AN XY:

74280

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

ACER3-related disorder

Benign:1

Benign, no assertion criteria provided

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

-0.41

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over