NM_006821.6:c.457G>C

Variant names:

• chr14-73569697-G-C
• rs1455494870
• NM_006821.6:c.457G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006821.6(ACOT2):​c.457G>C​(p.Val153Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ACOT2 NM_006821.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.92
• Publications: 0 publications found

Genes affected

ACOT2 (HGNC:18431): (acyl-CoA thioesterase 2) This gene encodes a member of the acyl-CoA thioesterase protein family, and is one of four acyl-CoA hydrolase genes located in a cluster on chromosome 14. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

HEATR4 (HGNC:16761): (HEAT repeat containing 4) Predicted to enable oxidoreductase activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000258603 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.025054365).
• BP6: Variant 14-73569697-G-C is Benign according to our data. Variant chr14-73569697-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3481398.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006821.6. 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
	ACOT2	NM_006821.6	MANE Select	c.457G>C	p.Val153Leu	missense	Exon 1 of 3	NP_006812.3
	ACOT2	NM_001364178.1		c.457G>C	p.Val153Leu	missense	Exon 1 of 3	NP_001351107.1
	ACOT2	NM_001364177.1		c.52+301G>C		intron	N/A	NP_001351106.1	B3KSA0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOT2	ENST00000238651.10	TSL:1 MANE Select	c.457G>C	p.Val153Leu	missense	Exon 1 of 3	ENSP00000238651.5	P49753-1
	ACOT2	ENST00000613168.1	TSL:1	c.397G>C	p.Val133Leu	missense	Exon 1 of 3	ENSP00000477685.1	A0A087WT95
	ACOT2	ENST00000864002.1		c.457G>C	p.Val153Leu	missense	Exon 1 of 3	ENSP00000534061.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457308 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724960

African (AFR) AF: 0.00 AC: 0 AN: 33334

American (AMR) AF: 0.00 AC: 0 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4774

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110956

Other (OTH) AF: 0.00 AC: 0 AN: 60056

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.077
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.0040
DANN	Benign	0.41
DEOGEN2	Benign	0.0080	T
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.027	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.5	N
PhyloP100		-6.9
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.030
Sift	Benign	0.70	T
Sift4G	Benign	0.79	T
Polyphen		0.0	B
Vest4		0.034
MutPred		0.48		Gain of ubiquitination at K150 (P = 0.0523)
MVP		0.25
ClinPred		0.083	T
GERP RS		-6.9
PromoterAI		0.028	Neutral
Varity_R		0.083
gMVP		0.47
Mutation Taster		=98/2	polymorphism

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: rs1455494870; hg19: chr14-74036401;