chr16-20543195-T-G

Position:

• chr16-20543195-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001105069.2(ACSM2B):​c.1349A>C​(p.Lys450Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 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)
• Consequence: ACSM2B NM_001105069.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.455

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSM2B	NM_001105069.2	c.1349A>C	p.Lys450Thr	missense_variant	11/14	ENST00000329697.10
ACSM2B	NM_182617.4	c.1349A>C	p.Lys450Thr	missense_variant	12/15
ACSM2B	NM_001410902.1	c.1112A>C	p.Lys371Thr	missense_variant	10/13
ACSM2B	XR_001751899.3	n.1629A>C		non_coding_transcript_exon_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSM2B	ENST00000329697.10	c.1349A>C	p.Lys450Thr	missense_variant	11/14	1	NM_001105069.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jul 11, 2023

The c.1349A>C (p.K450T) alteration is located in exon 12 (coding exon 10) of the ACSM2B gene. This alteration results from a A to C substitution at nucleotide position 1349, causing the lysine (K) at amino acid position 450 to be replaced by a threonine (T). 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	0.21
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0087	T;T;.;T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.94	.;D;D;.;.
M_CAP	Benign	0.0085	T
MetaRNN	Uncertain	0.54	D;D;D;D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.3	M;M;.;M;M
MutationTaster	Benign	0.99	N;N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.6	N;.;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.040	D;.;D;D;D
Sift4G	Benign	0.11	T;T;T;T;T
Polyphen		0.65	P;P;.;P;P
Vest4		0.52
MutPred		0.55		Gain of phosphorylation at K450 (P = 0.025);Gain of phosphorylation at K450 (P = 0.025);.;Gain of phosphorylation at K450 (P = 0.025);Gain of phosphorylation at K450 (P = 0.025);
MVP		0.56
MPC		0.59
ClinPred		0.65	D
GERP RS		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-20554517;