16-20465718-A-T

Position:

• chr16-20465718-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSM2A	NM_001308172.2	c.379A>T	p.Ile127Phe	missense_variant	3/14	ENST00000573854.6	NP_001295101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSM2A	ENST00000573854.6	c.379A>T	p.Ile127Phe	missense_variant	3/14	1	NM_001308172.2	ENSP00000459451.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2023

The c.379A>T (p.I127F) alteration is located in exon 4 (coding exon 2) of the ACSM2A gene. This alteration results from a A to T substitution at nucleotide position 379, causing the isoleucine (I) at amino acid position 127 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;T;T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.82	T;T;.;.;.;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.28	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	.;.;L;L;L;L
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.4	.;N;.;D;.;D
REVEL	Benign	0.073
Sift	Benign	0.042	.;D;.;D;.;D
Sift4G	Uncertain	0.016	D;T;T;T;T;T
Polyphen		0.78	.;.;P;P;P;P
Vest4		0.22, 0.22, 0.22
MutPred		0.61		.;.;Loss of stability (P = 0.2178);Loss of stability (P = 0.2178);Loss of stability (P = 0.2178);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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-20477040;