Genetic Variant NM_018367.7:c.148G>A (chr11-76926601-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_018367.7(ACER3):c.148G>A(p.Gly50Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,457,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G50C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ACER3
NM_018367.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.49

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.761

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACER3	NM_018367.7	MANE Select	c.148G>A	p.Gly50Ser	missense	Exon 2 of 11	NP_060837.3
ACER3	NM_001300954.2		c.-209G>A		5_prime_UTR	Exon 2 of 11	NP_001287883.1	B7Z2V2
ACER3	NM_001300955.2		c.-85G>A		5_prime_UTR	Exon 2 of 10	NP_001287884.1	B7Z2V2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACER3	ENST00000532485.6	TSL:1 MANE Select	c.148G>A	p.Gly50Ser	missense	Exon 2 of 11	ENSP00000434480.1	Q9NUN7-1
ACER3	ENST00000278544.9	TSL:1	n.148G>A		non_coding_transcript_exon	Exon 2 of 11	ENSP00000278544.5	J3KN85
ACER3	ENST00000525194.5	TSL:1	n.*29G>A		non_coding_transcript_exon	Exon 3 of 11	ENSP00000432109.1	E9PKR3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000200

AC:

AN:

250398

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1457038

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

725076

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33422

American (AMR)

AF:

0.00

AC:

AN:

44584

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.000328

AC:

AN:

39596

South Asian (SAS)

AF:

0.00

AC:

AN:

85980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000542

AC:

AN:

1107984

Other (OTH)

AF:

0.00

AC:

AN:

60252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Uncertain

0.061

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.84

M_CAP

Benign

0.020

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.3

PhyloP100

7.5

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.44

Sift

Benign

0.093

Sift4G

Benign

0.33

Polyphen

1.0

Vest4

0.95

MutPred

0.74

Loss of catalytic residue at Q53 (P = 0.1431)

MVP

0.68

MPC

1.6

ClinPred

0.63

GERP RS

5.8

Varity_R

0.68

gMVP

0.80

Mutation Taster

=194/106

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over