rs1453019114

Variant names:

• chr17-50461682-A-T
• rs1453019114
• NM_025149.6:c.503A>T

Your query was ambiguous. Multiple possible variants found:

• chr17-50461682-A-T
• chr17-50461682-A-G

Variant summary

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

The NM_025149.6(ACSF2):​c.503A>T​(p.Lys168Met) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACSF2 NM_025149.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.485
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28503364).

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.503A>T	p.Lys168Met	missense	Exon 4 of 16	NP_079425.3
	ACSF2	NM_001288968.2		c.578A>T	p.Lys193Met	missense	Exon 5 of 17	NP_001275897.1	Q96CM8-2
	ACSF2	NM_001288969.2		c.464A>T	p.Lys155Met	missense	Exon 4 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.503A>T	p.Lys168Met	missense	Exon 4 of 16	ENSP00000300441.4	Q96CM8-1
	ACSF2	ENST00000427954.6	TSL:2	c.578A>T	p.Lys193Met	missense	Exon 5 of 17	ENSP00000401831.2	Q96CM8-2
	ACSF2	ENST00000942398.1		c.503A>T	p.Lys168Met	missense	Exon 4 of 17	ENSP00000612457.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.17
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		0.48
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.24
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.023	D
Polyphen		0.98	D
Vest4		0.22
MutPred		0.59		Loss of ubiquitination at K168 (P = 0.0446)
MVP		0.56
MPC		1.3
ClinPred		0.99	D
GERP RS		0.79
Varity_R		0.50
gMVP		0.52

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: rs1453019114; hg19: chr17-48539043;