Genetic Variant ACSM2B:p.Trp442Arg (chr16-20543220-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001105069.2(ACSM2B):c.1324T>C(p.Trp442Arg) variant causes a missense change. The variant allele was found at a frequency of 0.003 in 1,613,870 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 8 hom. )

Consequence

ACSM2B
NM_001105069.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.99

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011591315).

BP6

Variant 16-20543220-A-G is Benign according to our data. Variant chr16-20543220-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3777764.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSM2B	NM_001105069.2 link	c.1324T>C	p.Trp442Arg	missense_variant	Exon 11 of 14	ENST00000329697.10	NP_001098539.1	Q68CK6
ACSM2B	NM_182617.4 link	c.1324T>C	p.Trp442Arg	missense_variant	Exon 12 of 15		NP_872423.3	Q68CK6
ACSM2B	NM_001410902.1 link	c.1087T>C	p.Trp363Arg	missense_variant	Exon 10 of 13		NP_001397831.1
ACSM2B	XR_001751899.3 link	n.1604T>C		non_coding_transcript_exon_variant	Exon 12 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSM2B	ENST00000329697.10 link	c.1324T>C	p.Trp442Arg	missense_variant	Exon 11 of 14	1	NM_001105069.2	ENSP00000327453.6		Q68CK6

Frequencies

GnomAD3 genomes

AF:

0.00331

AC:

503

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000581

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000719

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0212

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00340

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00343

AC:

861

AN:

251158

Hom.:

AF XY:

0.00354

AC XY:

480

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00173

Gnomad FIN exome

AF:

0.0201

Gnomad NFE exome

AF:

0.00295

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00297

AC:

4345

AN:

1461664

Hom.:

Cov.:

AF XY:

0.00296

AC XY:

2153

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00145

Gnomad4 FIN exome

AF:

0.0203

Gnomad4 NFE exome

AF:

0.00268

Gnomad4 OTH exome

AF:

0.00215

GnomAD4 genome

AF:

0.00330

AC:

503

AN:

152206

Hom.:

Cov.:

AF XY:

0.00404

AC XY:

301

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000579

Gnomad4 AMR

AF:

0.000718

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0212

Gnomad4 NFE

AF:

0.00340

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00293

Hom.:

Bravo

AF:

0.00157

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00322

AC:

391

EpiCase

AF:

0.00153

EpiControl

AF:

0.00202

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ACSM2B: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.065

T;T;.;T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.69

.;T;T;.;.

MetaRNN

Benign

0.012

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

M;M;.;M;M

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-6.2

D;.;D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0010

D;.;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D;D

Polyphen

0.066

B;B;.;B;B

Vest4

0.68

MutPred

0.78

Gain of methylation at W442 (P = 0.01);Gain of methylation at W442 (P = 0.01);.;Gain of methylation at W442 (P = 0.01);Gain of methylation at W442 (P = 0.01);

MVP

0.46

MPC

0.43

ClinPred

0.14

GERP RS

3.3

Varity_R

0.72

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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