16-20465718-A-T

Variant names:

• chr16-20465718-A-T
• NM_001308172.2:c.379A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001308172.2(ACSM2A):​c.379A>T​(p.Ile127Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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)
• Consequence: ACSM2A NM_001308172.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2774055).

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.379A>T	p.Ile127Phe	missense	Exon 3 of 14	NP_001295101.1	Q08AH3
	ACSM2A	NM_001308954.2		c.379A>T	p.Ile127Phe	missense	Exon 4 of 15	NP_001295883.1	Q08AH3
	ACSM2A	NM_001308169.2		c.142A>T	p.Ile48Phe	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.379A>T	p.Ile127Phe	missense	Exon 3 of 14	ENSP00000459451.1	Q08AH3
	ACSM2A	ENST00000219054.10	TSL:1	c.379A>T	p.Ile127Phe	missense	Exon 4 of 15	ENSP00000219054.6	Q08AH3
	ACSM2A	ENST00000396104.2	TSL:1	c.379A>T	p.Ile127Phe	missense	Exon 2 of 13	ENSP00000379411.2	Q08AH3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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	0.13
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.6
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.073
Sift	Benign	0.042	D
Sift4G	Uncertain	0.016	D
Polyphen		0.78	P
Vest4		0.22
MutPred		0.61		Loss of stability (P = 0.2178)
MVP		0.40
MPC		0.48
ClinPred		0.67	D
GERP RS		1.4
Varity_R		0.43
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

hg19: chr16-20477040;