16-20542972-T-G

Variant names:

• chr16-20542972-T-G
• rs766265299
• NM_001105069.2:c.1451A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001105069.2(ACSM2B):​c.1451A>C​(p.Lys484Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,568 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K484R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ACSM2B NM_001105069.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.16
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105069.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSM2B	NM_001105069.2	MANE Select	c.1451A>C	p.Lys484Thr	missense	Exon 12 of 14	NP_001098539.1	Q68CK6
	ACSM2B	NM_182617.4		c.1451A>C	p.Lys484Thr	missense	Exon 13 of 15	NP_872423.3
	ACSM2B	NM_001410902.1		c.1214A>C	p.Lys405Thr	missense	Exon 11 of 13	NP_001397831.1	H3BTX9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSM2B	ENST00000329697.10	TSL:1 MANE Select	c.1451A>C	p.Lys484Thr	missense	Exon 12 of 14	ENSP00000327453.6	Q68CK6
	ACSM2B	ENST00000414188.6	TSL:1	c.1451A>C	p.Lys484Thr	missense	Exon 11 of 13	ENSP00000390378.3	Q68CK6
	ACSM2B	ENST00000567001.5	TSL:1	c.1451A>C	p.Lys484Thr	missense	Exon 13 of 15	ENSP00000456378.1	Q68CK6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461568 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727106

African (AFR) AF: 0.00 AC: 0 AN: 33380

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111838

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0073	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.26	N
PhyloP100		6.2
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.086	B
Vest4		0.44
MutPred		0.59		Loss of ubiquitination at K484 (P = 0.0381)
MVP		0.53
MPC		0.28
ClinPred		0.81	D
GERP RS		3.1
Varity_R		0.28
gMVP		0.37
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs766265299; hg19: chr16-20554294;