16-20640516-T-A

Position:

• chr16-20640516-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001318890.3(ACSM1):​c.1061A>T​(p.Glu354Val) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACSM1 NM_001318890.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.05

Genes affected

ACSM1 (HGNC:18049): (acyl-CoA synthetase medium chain family member 1) Enables CoA-ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACSM3 (HGNC:10522): (acyl-CoA synthetase medium chain family member 3) Enables butyrate-CoA ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrion. Implicated in IgA glomerulonephritis. Biomarker of ulcerative colitis. [provided by Alliance of Genome Resources, Apr 2022]

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=0.2898651).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSM1	NM_001318890.3	c.1061A>T	p.Glu354Val	missense_variant	8/14	ENST00000520010.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSM1	ENST00000520010.6	c.1061A>T	p.Glu354Val	missense_variant	8/14	1	NM_001318890.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Nov 03, 2023

The c.1061A>T (p.E354V) alteration is located in exon 7 (coding exon 7) of the ACSM1 gene. This alteration results from a A to T substitution at nucleotide position 1061, causing the glutamic acid (E) at amino acid position 354 to be replaced by a valine (V). 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	0.18
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.086	T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.55	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N;N
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Benign	0.13
Sift	Benign	0.26	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.59	P;P
Vest4		0.36
MutPred		0.56		Loss of disorder (P = 0.0022);Loss of disorder (P = 0.0022);
MVP		0.66
MPC		0.16
ClinPred		0.33	T
GERP RS		3.6
Varity_R		0.25
gMVP		0.80

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-20651838;