14-73569275-C-T

Variant names:

• chr14-73569275-C-T
• NM_006821.6:c.35C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006821.6(ACOT2):​c.35C>T​(p.Ser12Leu) 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. 14/20 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: ACOT2 NM_006821.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.399

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.090845615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACOT2	NM_006821.6	c.35C>T	p.Ser12Leu	missense_variant	Exon 1 of 3	ENST00000238651.10	NP_006812.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACOT2	ENST00000238651.10	c.35C>T	p.Ser12Leu	missense_variant	Exon 1 of 3	1	NM_006821.6	ENSP00000238651.5
ACOT2	ENST00000538782.2	n.-23-3C>T		splice_region_variant, intron_variant	Intron 1 of 3	2		ENSP00000440961.2
ENSG00000258603	ENST00000664243.1	n.63-11303G>A		intron_variant	Intron 1 of 1
ACOT2	ENST00000613168.1	c.-26C>T		upstream_gene_variant		1		ENSP00000477685.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.35C>T (p.S12L) alteration is located in exon 1 (coding exon 1) of the ACOT2 gene. This alteration results from a C to T substitution at nucleotide position 35, causing the serine (S) at amino acid position 12 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.044
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.059	T
Polyphen		0.27	B
Vest4		0.30
MutPred		0.21		Loss of disorder (P = 0.0165);
MVP		0.38
ClinPred		0.16	T
GERP RS		1.0
Varity_R		0.067
gMVP		0.14

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-74035979;