Variant 11-76926607-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018367.7(ACER3):c.154G>A(p.Val52Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 1,598,032 control chromosomes in the GnomAD database, including 413,418 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35589 hom., cov: 32)

Exomes 𝑓: 0.72 ( 377829 hom. )

Consequence

ACER3
NM_018367.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.26

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3478816E-6).

BP6

Variant 11-76926607-G-A is Benign according to our data. Variant chr11-76926607-G-A is described in ClinVar as [Benign]. Clinvar id is 1165287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.734 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.154G>A	p.Val52Ile	missense_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.154G>A	p.Val52Ile	missense_variant	2/11	1	NM_018367.7	P1	Q9NUN7-1

Frequencies

GnomAD3 genomes

AF:

0.681

AC:

103348

AN:

151852

Hom.:

35557

Cov.:

show subpopulations

Gnomad AFR

AF:

0.633

Gnomad AMI

AF:

0.789

Gnomad AMR

AF:

0.549

Gnomad ASJ

AF:

0.744

Gnomad EAS

AF:

0.613

Gnomad SAS

AF:

0.624

Gnomad FIN

AF:

0.711

Gnomad MID

AF:

0.690

Gnomad NFE

AF:

0.739

Gnomad OTH

AF:

0.663

GnomAD3 exomes

AF:

0.671

AC:

166964

AN:

248700

Hom.:

57627

AF XY:

0.678

AC XY:

91210

AN XY:

134480

show subpopulations

Gnomad AFR exome

AF:

0.635

Gnomad AMR exome

AF:

0.470

Gnomad ASJ exome

AF:

0.752

Gnomad EAS exome

AF:

0.629

Gnomad SAS exome

AF:

0.638

Gnomad FIN exome

AF:

0.710

Gnomad NFE exome

AF:

0.738

Gnomad OTH exome

AF:

0.682

GnomAD4 exome

AF:

0.719

AC:

1039821

AN:

1446060

Hom.:

377829

Cov.:

AF XY:

0.718

AC XY:

516996

AN XY:

719892

show subpopulations

Gnomad4 AFR exome

AF:

0.631

Gnomad4 AMR exome

AF:

0.479

Gnomad4 ASJ exome

AF:

0.750

Gnomad4 EAS exome

AF:

0.639

Gnomad4 SAS exome

AF:

0.638

Gnomad4 FIN exome

AF:

0.710

Gnomad4 NFE exome

AF:

0.741

Gnomad4 OTH exome

AF:

0.705

GnomAD4 genome

AF:

0.681

AC:

103433

AN:

151972

Hom.:

35589

Cov.:

AF XY:

0.673

AC XY:

49989

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.634

Gnomad4 AMR

AF:

0.549

Gnomad4 ASJ

AF:

0.744

Gnomad4 EAS

AF:

0.613

Gnomad4 SAS

AF:

0.623

Gnomad4 FIN

AF:

0.711

Gnomad4 NFE

AF:

0.739

Gnomad4 OTH

AF:

0.665

Alfa

AF:

0.717

Hom.:

44543

Bravo

AF:

0.670

TwinsUK

AF:

0.742

AC:

2753

ALSPAC

AF:

0.748

AC:

2881

ESP6500AA

AF:

0.644

AC:

2835

ESP6500EA

AF:

0.736

AC:

6318

ExAC

AF:

0.678

AC:

82341

Asia WGS

AF:

0.587

AC:

2045

AN:

3478

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

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

5.0

DANN

Benign

0.37

DEOGEN2

Benign

0.21

.;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.092

T;T

MetaRNN

Benign

0.0000013

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.94

.;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.42

PROVEAN

Benign

0.31

N;N

REVEL

Benign

0.025

Sift

Benign

1.0

T;T

Sift4G

Benign

0.59

T;T

Polyphen

0.0

.;B

Vest4

0.087

MPC

0.54

ClinPred

0.00053

GERP RS

2.1

Varity_R

0.055

gMVP

0.050

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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