chr16-20483086-C-T

Variant names:

• chr16-20483086-C-T
• rs1133607
• NM_001308172.2:c.1538C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM1 BP4_Strong BA1

The NM_001308172.2(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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1178 hom., cov: 31)
  • Exomes 𝑓: 0.11 (9681 hom.)
• Consequence: ACSM2A NM_001308172.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.57
• Publications: 13 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity ACS2A_HUMAN
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308172.2. 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
	ACSM2A	NM_001308172.2	MANE Select	c.1538C>T	p.Ser513Leu	missense	Exon 13 of 14	NP_001295101.1	Q08AH3
	ACSM2A	NM_001308954.2		c.1538C>T	p.Ser513Leu	missense	Exon 14 of 15	NP_001295883.1	Q08AH3
	ACSM2A	NM_001308169.2		c.1301C>T	p.Ser434Leu	missense	Exon 12 of 13	NP_001295098.1	F5GWL3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSM2A	ENST00000573854.6	TSL:1 MANE Select	c.1538C>T	p.Ser513Leu	missense	Exon 13 of 14	ENSP00000459451.1	Q08AH3
	ACSM2A	ENST00000219054.10	TSL:1	c.1538C>T	p.Ser513Leu	missense	Exon 14 of 15	ENSP00000219054.6	Q08AH3
	ACSM2A	ENST00000396104.2	TSL:1	c.1538C>T	p.Ser513Leu	missense	Exon 12 of 13	ENSP00000379411.2	Q08AH3

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

GnomAD2 exomes AF: 0.128 AC: 32100 AN: 251472 AF XY: 0.130

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 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

African (AFR) AF: 0.132 AC: 4434 AN: 33470

American (AMR) AF: 0.147 AC: 6559 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 2950 AN: 26124

East Asian (EAS) AF: 0.223 AC: 8838 AN: 39684

South Asian (SAS) AF: 0.200 AC: 17242 AN: 86244

European-Finnish (FIN) AF: 0.107 AC: 5689 AN: 53386

Middle Eastern (MID) AF: 0.137 AC: 787 AN: 5764

European-Non Finnish (NFE) AF: 0.0955 AC: 106177 AN: 1111844

Other (OTH) AF: 0.112 AC: 6734 AN: 60376

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

African (AFR) AF: 0.124 AC: 5146 AN: 41496

American (AMR) AF: 0.132 AC: 2020 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 402 AN: 3468

East Asian (EAS) AF: 0.201 AC: 1036 AN: 5154

South Asian (SAS) AF: 0.193 AC: 929 AN: 4808

European-Finnish (FIN) AF: 0.111 AC: 1176 AN: 10586

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0980 AC: 6661 AN: 67998

Other (OTH) AF: 0.125 AC: 264 AN: 2106

Alfa AF: 0.105 Hom.: 643

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 v4.9

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
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.6
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.094
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.0010	B
Vest4		0.13
MPC		0.19
ClinPred		0.028	T
GERP RS		3.3
Varity_R		0.51
gMVP		0.17
Mutation Taster		=96/4	polymorphism (auto)

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