dbSNP rs142474503: ACSM2A:p.Ala60Gly (chr16-20465518-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001308172.2(ACSM2A):c.179C>G(p.Ala60Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ACSM2A
NM_001308172.2 missense, splice_region

Scores

Splicing: ADA: 0.00005989

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.12

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.057154775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSM2A	NM_001308172.2 link	c.179C>G	p.Ala60Gly	missense_variant, splice_region_variant	Exon 3 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.179C>G	p.Ala60Gly	missense_variant, splice_region_variant	Exon 3 of 14	1	NM_001308172.2	ENSP00000459451.1		Q08AH3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461556

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727066

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

6.9

DANN

Benign

0.88

DEOGEN2

Benign

0.065

T;T;T;T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.11

T;.;.;.;T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.057

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.2

.;M;M;M;.;M

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.2

.;.;N;.;.;N

REVEL

Benign

0.057

Sift

Benign

0.25

.;.;T;.;.;T

Sift4G

Benign

0.19

T;T;T;T;T;T

Polyphen

0.0080

.;B;B;B;.;B

Vest4

0.21, 0.21, 0.21

MutPred

0.32

Gain of ubiquitination at K59 (P = 0.0645);Gain of ubiquitination at K59 (P = 0.0645);Gain of ubiquitination at K59 (P = 0.0645);Gain of ubiquitination at K59 (P = 0.0645);Gain of ubiquitination at K59 (P = 0.0645);Gain of ubiquitination at K59 (P = 0.0645);

MVP

0.061

MPC

0.31

ClinPred

0.39

GERP RS

-0.45

Varity_R

0.18

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000060

dbscSNV1_RF

Benign

0.018

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over