16-20640532-G-C

Variant names:

• chr16-20640532-G-C
• NM_001318890.3:c.1045C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001318890.3(ACSM1):​c.1045C>G​(p.Pro349Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P349S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ACSM1 NM_001318890.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSM1	NM_001318890.3	c.1045C>G	p.Pro349Ala	missense_variant	Exon 8 of 14	ENST00000520010.6	NP_001305819.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSM1	ENST00000520010.6	c.1045C>G	p.Pro349Ala	missense_variant	Exon 8 of 14	1	NM_001318890.3	ENSP00000428047.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461838 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.50	.;T
M_CAP	Benign	0.0073	T
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-6.5	D;D
REVEL	Benign	0.18
Sift	Uncertain	0.014	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.0030	B;B
Vest4		0.38
MutPred		0.68		Loss of ubiquitination at K350 (P = 0.0665);Loss of ubiquitination at K350 (P = 0.0665);
MVP		0.58
MPC		0.079
ClinPred		0.28	T
GERP RS		3.9
Varity_R		0.23
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-20651854;