16-20553787-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001105069.2(ACSM2B):c.730A>G(p.Met244Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ACSM2B NM_001105069.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.152

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04947862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSM2B	NM_001105069.2	c.730A>G	p.Met244Val	missense_variant	5/14	ENST00000329697.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSM2B	ENST00000329697.10	c.730A>G	p.Met244Val	missense_variant	5/14	1	NM_001105069.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457342 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724424

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.730A>G (p.M244V) alteration is located in exon 6 (coding exon 4) of the ACSM2B gene. This alteration results from a A to G substitution at nucleotide position 730, causing the methionine (M) at amino acid position 244 to be replaced by a valine (V). 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	0.084
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	9.9
Dann	Benign	0.65
DEOGEN2	Benign	0.0025	T;T;.;T;T;.;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.54	D
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.049	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.61	N;N;.;N;N;.;.
MutationTaster	Benign	0.75	N;N;N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.020	N;.;N;N;N;.;N
REVEL	Benign	0.024
Sift	Benign	1.0	T;.;T;T;T;.;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T
Polyphen		0.0010	B;B;.;B;B;.;.
Vest4		0.16
MutPred		0.44		Gain of ubiquitination at K241 (P = 0.0913);Gain of ubiquitination at K241 (P = 0.0913);.;Gain of ubiquitination at K241 (P = 0.0913);Gain of ubiquitination at K241 (P = 0.0913);.;.;
MVP		0.29
MPC		1.0
ClinPred		0.055	T
GERP RS		0.96
Varity_R		0.054
gMVP		0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-20565109;