chr16-20623556-T-C

Variant names:

• chr16-20623556-T-C
• NM_001318890.3:c.1664A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001318890.3(ACSM1):​c.1664A>G​(p.Glu555Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACSM1 NM_001318890.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.26
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3702472).

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.1664A>G	p.Glu555Gly	missense	Exon 14 of 14	NP_001305819.1	Q08AH1-1
	ACSM1	NM_052956.3		c.1664A>G	p.Glu555Gly	missense	Exon 13 of 13	NP_443188.2	Q08AH1-1
	ACSM1	NR_134918.2		n.1400A>G		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.1664A>G	p.Glu555Gly	missense	Exon 14 of 14	ENSP00000428047.1	Q08AH1-1
	ACSM1	ENST00000307493.8	TSL:1	c.1664A>G	p.Glu555Gly	missense	Exon 13 of 13	ENSP00000301956.3	Q08AH1-1
	ACSM1	ENST00000519745.5	TSL:1	n.*717A>G		non_coding_transcript_exon	Exon 11 of 11	ENSP00000428650.1	Q08AH1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.13
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.37	T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.3
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.20
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.026	D
Polyphen		0.97	D
Vest4		0.14
MutPred		0.29		Gain of glycosylation at S554 (P = 0.0264)
MVP		0.67
MPC		0.38
ClinPred		0.95	D
GERP RS		4.2
Varity_R		0.33
gMVP		0.34

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

hg19: chr16-20634878;