rs781233119

Variant names:

• chr16-20465595-C-A
• rs781233119
• NM_001308172.2:c.256C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-20465595-C-A
• chr16-20465595-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001308172.2(ACSM2A):​c.256C>A​(p.Leu86Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 15/22 in silico tools predict a benign 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.)
  • Failed GnomAD Quality Control
• Consequence: ACSM2A NM_001308172.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.579
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.256C>A	p.Leu86Met	missense	Exon 3 of 14	NP_001295101.1	Q08AH3
	ACSM2A	NM_001308954.2		c.256C>A	p.Leu86Met	missense	Exon 4 of 15	NP_001295883.1	Q08AH3
	ACSM2A	NM_001308169.2		c.19C>A	p.Leu7Met	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.256C>A	p.Leu86Met	missense	Exon 3 of 14	ENSP00000459451.1	Q08AH3
	ACSM2A	ENST00000219054.10	TSL:1	c.256C>A	p.Leu86Met	missense	Exon 4 of 15	ENSP00000219054.6	Q08AH3
	ACSM2A	ENST00000396104.2	TSL:1	c.256C>A	p.Leu86Met	missense	Exon 2 of 13	ENSP00000379411.2	Q08AH3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251160 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2 AN: 1461662 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727144

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44706

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

East Asian (EAS) AF: 0.0000504 AC: 2 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: 0.00 AC: 0 AN: 1111842

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000330 AC: 4

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	Benign	0.18
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.090	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.58
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.26
Sift	Benign	0.091	T
Sift4G	Benign	0.17	T
Polyphen		0.83	P
Vest4		0.53
MutPred		0.83		Gain of MoRF binding (P = 0.0783)
MVP		0.59
MPC		0.96
ClinPred		0.19	T
GERP RS		0.44
Varity_R		0.38
gMVP		0.55

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: rs781233119; hg19: chr16-20476917;