Variant 16-20546419-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001105069.2(ACSM2B):c.1154C>T(p.Thr385Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000407 in 1,608,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 0 hom. )

Consequence

ACSM2B
NM_001105069.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.405

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07596266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSM2B	NM_001105069.2 linkuse as main transcript	c.1154C>T	p.Thr385Met	missense_variant	9/14	ENST00000329697.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSM2B	ENST00000329697.10 linkuse as main transcript	c.1154C>T	p.Thr385Met	missense_variant	9/14	1	NM_001105069.2	P1

Frequencies

GnomAD3 genomes

AF:

0.000638

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000918

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000294

AC:

AN:

234896

Hom.:

AF XY:

0.000269

AC XY:

AN XY:

126258

show subpopulations

Gnomad AFR exome

AF:

0.000812

Gnomad AMR exome

AF:

0.0000928

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0000758

Gnomad FIN exome

AF:

0.0000973

Gnomad NFE exome

AF:

0.000438

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000382

AC:

557

AN:

1456408

Hom.:

Cov.:

AF XY:

0.000356

AC XY:

258

AN XY:

723854

show subpopulations

Gnomad4 AFR exome

AF:

0.000481

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000351

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.000447

Gnomad4 OTH exome

AF:

0.000416

GnomAD4 genome

AF:

0.000637

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000915

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000947

Hom.:

Bravo

AF:

0.000359

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.000701

AC:

ExAC

AF:

0.000346

AC:

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

Feb 02, 2022

The c.1154C>T (p.T385M) alteration is located in exon 10 (coding exon 8) of the ACSM2B gene. This alteration results from a C to T substitution at nucleotide position 1154, causing the threonine (T) at amino acid position 385 to be replaced by a methionine (M). 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

Benign

0.071

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.67

Cadd

Benign

2.0

Dann

Benign

0.74

DEOGEN2

Benign

0.0057

T;T;.;T;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.021

M_CAP

Benign

0.0067

MetaRNN

Benign

0.076

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;.;L;L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.57

N;.;N;N;N;.

REVEL

Benign

0.084

Sift

Benign

0.032

D;.;D;D;D;.

Sift4G

Uncertain

0.030

D;D;D;D;D;D

Polyphen

0.70

P;P;.;P;P;.

Vest4

0.23

MVP

0.12

MPC

0.62

ClinPred

0.016

GERP RS

-6.3

Varity_R

0.061

gMVP

0.33

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