16-20625481-T-G

Position:

• chr16-20625481-T-G

Variant summary

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

The NM_001318890.3(ACSM1):​c.1469A>C​(p.Glu490Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000752 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: ACSM1 NM_001318890.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.05

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSM1	NM_001318890.3	c.1469A>C	p.Glu490Ala	missense_variant	12/14	ENST00000520010.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSM1	ENST00000520010.6	c.1469A>C	p.Glu490Ala	missense_variant	12/14	1	NM_001318890.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000279 AC: 7 AN: 251216 Hom.: 0 AF XY: 0.0000368 AC XY: 5 AN XY: 135788

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000752 AC: 11 AN: 1461816 Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9 AN XY: 727210

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: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T
Eigen	Benign	0.091
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	.;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.79	N;N
MutationTaster	Benign	0.88	D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.72	P;P
Vest4		0.34
MutPred		0.54		Loss of disorder (P = 0.045);Loss of disorder (P = 0.045);
MVP		0.72
MPC		0.30
ClinPred		0.56	D
GERP RS		4.5
Varity_R		0.35
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs745581421; hg19: chr16-20636803;