NM_001105069.2:c.1460C>T

Variant names:

• chr16-20542963-G-A
• rs761525079
• NM_001105069.2:c.1460C>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001105069.2(ACSM2B):​c.1460C>T​(p.Ala487Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. A487D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: ACSM2B NM_001105069.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.96

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSM2B	NM_001105069.2	c.1460C>T	p.Ala487Val	missense_variant	Exon 12 of 14	ENST00000329697.10	NP_001098539.1
ACSM2B	NM_182617.4	c.1460C>T	p.Ala487Val	missense_variant	Exon 13 of 15		NP_872423.3
ACSM2B	NM_001410902.1	c.1223C>T	p.Ala408Val	missense_variant	Exon 11 of 13		NP_001397831.1
ACSM2B	XR_001751899.3	n.*212C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSM2B	ENST00000329697.10	c.1460C>T	p.Ala487Val	missense_variant	Exon 12 of 14	1	NM_001105069.2	ENSP00000327453.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251114 Hom.: 0 AF XY: 0.0000295 AC XY: 4 AN XY: 135718

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461572 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 727106

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: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	T;T;.;T;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.97	.;D;D;.;.
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.88	D;D;D;D;D
MetaSVM	Uncertain	0.079	D
MutationAssessor	Uncertain	2.4	M;M;.;M;M
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.4	D;.;D;D;D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0070	D;.;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D
Polyphen		1.0	D;D;.;D;D
Vest4		0.60
MutPred		0.77		Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);.;Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);
MVP		0.76
MPC		0.65
ClinPred		0.91	D
GERP RS		3.1
Varity_R		0.29
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs761525079; hg19: chr16-20554285;