rs745993663

Variant names:

• chr16-20465644-G-A
• rs745993663
• NM_001308172.2:c.305G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-20465644-G-A
• chr16-20465644-G-T

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.305G>A​(p.Gly102Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ACSM2A NM_001308172.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.61
• 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, 0.915

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.305G>A	p.Gly102Asp	missense	Exon 3 of 14	NP_001295101.1	Q08AH3
	ACSM2A	NM_001308954.2		c.305G>A	p.Gly102Asp	missense	Exon 4 of 15	NP_001295883.1	Q08AH3
	ACSM2A	NM_001308169.2		c.68G>A	p.Gly23Asp	missense	Exon 2 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.305G>A	p.Gly102Asp	missense	Exon 3 of 14	ENSP00000459451.1	Q08AH3
	ACSM2A	ENST00000219054.10	TSL:1	c.305G>A	p.Gly102Asp	missense	Exon 4 of 15	ENSP00000219054.6	Q08AH3
	ACSM2A	ENST00000396104.2	TSL:1	c.305G>A	p.Gly102Asp	missense	Exon 2 of 13	ENSP00000379411.2	Q08AH3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461666 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727140

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111836

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

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	Benign	0.12
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.12
Eigen_PC	Benign	-0.049
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Benign	-0.29	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		2.6
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.90		Loss of catalytic residue at C101 (P = 0.0785)
MVP		0.72
MPC		1.0
ClinPred		0.86	D
GERP RS		1.7
Varity_R		0.45
gMVP		0.76

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: rs745993663; hg19: chr16-20476966;