Variant 16-20465616-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001308172.2(ACSM2A):c.277G>A(p.Ala93Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000629 in 1,613,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00067 ( 0 hom. )

Consequence

ACSM2A
NM_001308172.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

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:

ACSM2A (HGNC:):

ACSM2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.113450974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSM2A	NM_001308172.2 linkuse as main transcript	c.277G>A	p.Ala93Thr	missense_variant	3/14	ENST00000573854.6	NP_001295101.1	Q08AH3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSM2A	ENST00000573854.6 linkuse as main transcript	c.277G>A	p.Ala93Thr	missense_variant	3/14	1	NM_001308172.2	ENSP00000459451.1		Q08AH3

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000195

AC:

AN:

251178

Hom.:

AF XY:

0.000184

AC XY:

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000397

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000666

AC:

973

AN:

1461672

Hom.:

Cov.:

AF XY:

0.000615

AC XY:

447

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000812

Gnomad4 OTH exome

AF:

0.00104

GnomAD4 genome

AF:

0.000276

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000101

Hom.:

Bravo

AF:

0.000332

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000181

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 07, 2024

The c.277G>A (p.A93T) alteration is located in exon 4 (coding exon 2) of the ACSM2A gene. This alteration results from a G to A substitution at nucleotide position 277, causing the alanine (A) at amino acid position 93 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.033

.;T;T;T;T;T;T;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.84

T;T;T;.;.;.;T;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.11

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.94

.;.;.;L;L;L;.;L

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.9

.;.;N;.;N;.;.;N

REVEL

Benign

0.092

Sift

Benign

0.22

.;.;T;.;T;.;.;T

Sift4G

Benign

0.38

T;T;T;T;T;T;T;T

Polyphen

0.27

.;.;.;B;B;B;.;B

Vest4

0.14, 0.14

MVP

0.17

MPC

0.31

ClinPred

0.025

GERP RS

1.5

Varity_R

0.29

gMVP

0.32

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over