17-50462464-C-T

Variant names:

• chr17-50462464-C-T
• rs1218655049
• NM_025149.6:c.671C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_025149.6(ACSF2):​c.671C>T​(p.Pro224Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,461,074 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: ACSF2 NM_025149.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.12
• Publications: 1 publications found

Genes affected

ACSF2 (HGNC:26101): (acyl-CoA synthetase family member 2) Enables medium-chain fatty acid-CoA ligase activity. Predicted to be involved in fatty acid metabolic process. Predicted to be located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025149.6. 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
	ACSF2	NM_025149.6	MANE Select	c.671C>T	p.Pro224Leu	missense	Exon 6 of 16	NP_079425.3
	ACSF2	NM_001288968.2		c.746C>T	p.Pro249Leu	missense	Exon 7 of 17	NP_001275897.1	Q96CM8-2
	ACSF2	NM_001288969.2		c.632C>T	p.Pro211Leu	missense	Exon 6 of 16	NP_001275898.1	Q96CM8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSF2	ENST00000300441.9	TSL:1 MANE Select	c.671C>T	p.Pro224Leu	missense	Exon 6 of 16	ENSP00000300441.4	Q96CM8-1
	ACSF2	ENST00000427954.6	TSL:2	c.746C>T	p.Pro249Leu	missense	Exon 7 of 17	ENSP00000401831.2	Q96CM8-2
	ACSF2	ENST00000942398.1		c.671C>T	p.Pro224Leu	missense	Exon 6 of 17	ENSP00000612457.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251228 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461074 Hom.: 0 Cov.: 39 AF XY: 0.0000124 AC XY: 9 AN XY: 726876

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.0000448 AC: 2 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39662

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111516

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

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	0.11
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Benign	0.27
Sift	Benign	0.033	D
Sift4G	Uncertain	0.031	D
Polyphen		0.13	B
Vest4		0.80
MutPred		0.47		Loss of glycosylation at P224 (P = 0.1036)
MVP		0.44
MPC		0.68
ClinPred		0.98	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.62
Mutation Taster		=26/74	disease causing

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

Other links and lift over

dbSNP: rs1218655049; hg19: chr17-48539825; COSMIC: COSV51973017; COSMIC: COSV51973017;