16-20623529-A-G

Variant names:

• chr16-20623529-A-G
• rs142695037
• NM_001318890.3:c.1691T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001318890.3(ACSM1):​c.1691T>C​(p.Ile564Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000415 in 1,614,026 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: ACSM1 NM_001318890.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.13
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

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.1691T>C	p.Ile564Thr	missense	Exon 14 of 14	NP_001305819.1	Q08AH1-1
	ACSM1	NM_052956.3		c.1691T>C	p.Ile564Thr	missense	Exon 13 of 13	NP_443188.2	Q08AH1-1
	ACSM1	NR_134918.2		n.1427T>C		non_coding_transcript_exon	Exon 11 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSM1	ENST00000520010.6	TSL:1 MANE Select	c.1691T>C	p.Ile564Thr	missense	Exon 14 of 14	ENSP00000428047.1	Q08AH1-1
	ACSM1	ENST00000307493.8	TSL:1	c.1691T>C	p.Ile564Thr	missense	Exon 13 of 13	ENSP00000301956.3	Q08AH1-1
	ACSM1	ENST00000519745.5	TSL:1	n.*744T>C		non_coding_transcript_exon	Exon 11 of 11	ENSP00000428650.1	Q08AH1-2

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000477 AC: 12 AN: 251460 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000335 AC: 49 AN: 1461852 Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24 AN XY: 727222

African (AFR) AF: 0.000568 AC: 19 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1111984

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74352

African (AFR) AF: 0.000434 AC: 18 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000132 Hom.: 0

Bravo AF: 0.000140

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000576 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.32
Sift	Benign	0.068	T
Sift4G	Uncertain	0.022	D
Polyphen		1.0	D
Vest4		0.74
MVP		0.79
MPC		0.49
ClinPred		0.38	T
GERP RS		2.9
Varity_R		0.34
gMVP		0.51
Mutation Taster		=77/23	polymorphism

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: rs142695037; hg19: chr16-20634851; COSMIC: COSV54636228; COSMIC: COSV54636228;