rs776668743

Variant names:

• chr16-20460269-A-C
• rs776668743
• NM_001308172.2:c.155A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-20460269-A-C
• chr16-20460269-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001308172.2(ACSM2A):​c.155A>C​(p.Asp52Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: ACSM2A NM_001308172.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.75
• Publications: 0 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.846

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.155A>C	p.Asp52Ala	missense	Exon 2 of 14	NP_001295101.1	Q08AH3
	ACSM2A	NM_001308954.2		c.155A>C	p.Asp52Ala	missense	Exon 3 of 15	NP_001295883.1	Q08AH3
	ACSM2A	NM_001308169.2		c.-60-5248A>C		intron	N/A	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.155A>C	p.Asp52Ala	missense	Exon 2 of 14	ENSP00000459451.1	Q08AH3
	ACSM2A	ENST00000219054.10	TSL:1	c.155A>C	p.Asp52Ala	missense	Exon 3 of 15	ENSP00000219054.6	Q08AH3
	ACSM2A	ENST00000396104.2	TSL:1	c.155A>C	p.Asp52Ala	missense	Exon 1 of 13	ENSP00000379411.2	Q08AH3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.47	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		3.8
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-7.1	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.71		Loss of catalytic residue at D52 (P = 0.0281)
MVP		0.60
MPC		1.0
ClinPred		0.99	D
GERP RS		2.7
PromoterAI		-0.010	Neutral
Varity_R		0.68
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs776668743; hg19: chr16-20471591;