Variant 16-20483086-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1178 hom., cov: 31)

Exomes 𝑓: 0.11 ( 9681 hom. )

Consequence

ACSM2A
NM_001308172.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.57

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
ACSM2A	NM_001308172.2 link	c.1538C>T	p.Ser513Leu	missense_variant	Exon 13 of 14	ENST00000573854.6	NP_001295101.1	Q08AH3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSM2A	ENST00000573854.6 link	c.1538C>T	p.Ser513Leu	missense_variant	Exon 13 of 14	1	NM_001308172.2	ENSP00000459451.1		Q08AH3

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17768

AN:

151990

Hom.:

1175

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.112

AC XY:

81179

AN XY:

727086

show subpopulations

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.:

AF XY:

0.121

AC XY:

8992

AN XY:

74344

show subpopulations

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

BayesDel_noAF

Benign

-0.47

CADD

Benign

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

LIST_S2

Benign

0.15

T;.;.;.;T

MetaRNN

Benign

0.0016

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;L;L;L;L

PrimateAI

Benign

0.38

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over