Variant 16-20543162-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_001105069.2(ACSM2B):c.1382G>A(p.Arg461Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000496 in 1,613,680 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R461W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

ACSM2B
NM_001105069.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.95

Variant links:

Genes affected

ACSM2B (HGNC:30931): (acyl-CoA synthetase medium chain family member 2B) Enables benzoate-CoA ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACSM2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity ACS2B_HUMAN

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ACSM2B	NM_001105069.2 linkuse as main transcript	c.1382G>A	p.Arg461Gln	missense_variant	11/14	ENST00000329697.10
ACSM2B	NM_182617.4 linkuse as main transcript	c.1382G>A	p.Arg461Gln	missense_variant	12/15
ACSM2B	NM_001410902.1 linkuse as main transcript	c.1145G>A	p.Arg382Gln	missense_variant	10/13
ACSM2B	XR_001751899.3 linkuse as main transcript			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSM2B	ENST00000329697.10 linkuse as main transcript	c.1382G>A	p.Arg461Gln	missense_variant	11/14	1	NM_001105069.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000796

AC:

AN:

251174

Hom.:

AF XY:

0.0000810

AC XY:

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000499

AC:

AN:

1461640

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152040

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000197

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 18, 2021

The c.1382G>A (p.R461Q) alteration is located in exon 12 (coding exon 10) of the ACSM2B gene. This alteration results from a G to A substitution at nucleotide position 1382, causing the arginine (R) at amino acid position 461 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Pathogenic

0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;T;.;T;T

Eigen

Benign

-0.047

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.22

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.73

D;D;D;D;D

MetaSVM

Uncertain

0.70

MutationAssessor

Pathogenic

4.1

H;H;.;H;H

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.5

D;.;D;D;D

REVEL

Uncertain

0.62

Sift

Uncertain

0.0010

D;.;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D;D

Polyphen

1.0

D;D;.;D;D

Vest4

0.80

MVP

0.75

MPC

0.82

ClinPred

0.82

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.93

gMVP

0.84

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