16-20483086-C-T

Position:

• chr16-20483086-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000573854.6(ACSM2A):​c.1538C>T​(p.Ser513Leu) variant causes a missense change. The variant allele was found at a frequency of 0.11 in 1,613,714 control chromosomes in the GnomAD database, including 10,859 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.12 (1178 hom., cov: 31)
  • Exomes 𝑓: 0.11 (9681 hom.)
• Consequence: ACSM2A ENST00000573854.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.57

Genes affected

ACSM2A (HGNC:32017): (acyl-CoA synthetase medium chain family member 2A) This gene encodes a mitochondrial acyl-coenzyme A synthetase that is specific for medium chain fatty acids. These enzymes catalyze fatty acid activation, the first step of fatty acid metabolism, through the transfer of acyl-CoA. These enzymes also participate in the glycine conjugation pathway in the detoxification of xenobiotics such as benzoate and ibuprofen. Expression levels of this gene in the kidney may be correlated with kidney function. This gene and its paralog ACSM2B (Gene ID: 348158), both present on chromosome 16, likely arose from a chromosomal duplication event. [provided by RefSeq, May 2017]

ACSM2A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016130507).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSM2A	NM_001308172.2	c.1538C>T	p.Ser513Leu	missense_variant	13/14	ENST00000573854.6	NP_001295101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSM2A	ENST00000573854.6	c.1538C>T	p.Ser513Leu	missense_variant	13/14	1	NM_001308172.2	ENSP00000459451.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17768 AN: 151990 Hom.: 1175 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0979

Gnomad OTH AF: 0.127

GnomAD3 exomes AF: 0.128 AC: 32100 AN: 251472 Hom.: 2395 AF XY: 0.130 AC XY: 17699 AN XY: 135910

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.199

Gnomad SAS exome AF: 0.196

Gnomad FIN exome AF: 0.108

Gnomad NFE exome AF: 0.0967

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.109 AC: 159410 AN: 1461606 Hom.: 9681 Cov.: 31 AF XY: 0.112 AC XY: 81179 AN XY: 727086

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.223

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.0955

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.117 AC: 17786 AN: 152108 Hom.: 1178 Cov.: 31 AF XY: 0.121 AC XY: 8992 AN XY: 74344

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.0980

Gnomad4 OTH AF: 0.125

Alfa AF: 0.103 Hom.: 352

Bravo AF: 0.117

TwinsUK AF: 0.104 AC: 385

ALSPAC AF: 0.0952 AC: 367

ESP6500AA AF: 0.125 AC: 551

ESP6500EA AF: 0.101 AC: 872

ExAC AF: 0.128 AC: 15506

Asia WGS AF: 0.161 AC: 558 AN: 3478

EpiCase AF: 0.0953

EpiControl AF: 0.0949

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T;T;T;T;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.15	T;.;.;.;T
MetaRNN	Benign	0.0016	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	.;L;L;L;L
MutationTaster	Benign	0.90	P;P;P;P;P
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.5	D;.;D;.;D
REVEL	Benign	0.094
Sift	Uncertain	0.0080	D;.;D;.;D
Sift4G	Uncertain	0.0050	D;D;D;D;D
Polyphen		0.0010	.;B;B;B;B
Vest4		0.13
MPC		0.19
ClinPred		0.028	T
GERP RS		3.3
Varity_R		0.51
gMVP		0.17

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

Other links and lift over

dbSNP: rs1133607; hg19: chr16-20494408; COSMIC: COSV54584642; COSMIC: COSV54584642;