NM_001318890.3:c.992+941T>C

Variant names:

• chr16-20660853-A-G
• rs163275
• NM_001318890.3:c.992+941T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318890.3(ACSM1):​c.992+941T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,028 control chromosomes in the GnomAD database, including 14,000 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (14000 hom., cov: 32)
• Consequence: ACSM1 NM_001318890.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318890.3. 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
	ACSM1	NM_001318890.3	MANE Select	c.992+941T>C		intron	N/A	NP_001305819.1	Q08AH1-1
	ACSM1	NM_052956.3		c.992+941T>C		intron	N/A	NP_443188.2	Q08AH1-1
	ACSM1	NR_134918.2		n.1121+941T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSM1	ENST00000520010.6	TSL:1 MANE Select	c.992+941T>C		intron	N/A	ENSP00000428047.1	Q08AH1-1
	ACSM1	ENST00000307493.8	TSL:1	c.992+941T>C		intron	N/A	ENSP00000301956.3	Q08AH1-1
	ACSM1	ENST00000519745.5	TSL:1	n.*438+941T>C		intron	N/A	ENSP00000428650.1	Q08AH1-2

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61761 AN: 151910 Hom.: 13980 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.406

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.407 AC: 61836 AN: 152028 Hom.: 14000 Cov.: 32 AF XY: 0.409 AC XY: 30356 AN XY: 74294

African (AFR) AF: 0.535 AC: 22198 AN: 41478

American (AMR) AF: 0.358 AC: 5461 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1768 AN: 3466

East Asian (EAS) AF: 0.853 AC: 4405 AN: 5162

South Asian (SAS) AF: 0.540 AC: 2600 AN: 4818

European-Finnish (FIN) AF: 0.277 AC: 2922 AN: 10564

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21276 AN: 67954

Other (OTH) AF: 0.408 AC: 862 AN: 2112

Alfa AF: 0.353 Hom.: 5222

Bravo AF: 0.417

Asia WGS AF: 0.633 AC: 2198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	9.9
DANN	Benign	0.70
PhyloP100		0.093
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs163275; hg19: chr16-20672175;