chr14-73569311-C-G

Variant names:

• chr14-73569311-C-G
• NM_006821.6:c.71C>G

Variant summary

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

The NM_001364177.1(ACOT2):​c.-34C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ACOT2 NM_001364177.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.36

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=0.09164551).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACOT2	NM_006821.6	c.71C>G	p.Ser24Cys	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.71C>G	p.Ser24Cys	missense_variant	Exon 1 of 3	1	NM_006821.6	ENSP00000238651.5
ACOT2	ENST00000613168.1	c.11C>G	p.Ser4Cys	missense_variant	Exon 1 of 3	1		ENSP00000477685.1
ACOT2	ENST00000538782.2	n.11C>G		non_coding_transcript_exon_variant	Exon 2 of 4	2		ENSP00000440961.2
ENSG00000258603	ENST00000664243.1	n.63-11339G>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461662 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727128

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.71C>G (p.S24C) alteration is located in exon 1 (coding exon 1) of the ACOT2 gene. This alteration results from a C to G substitution at nucleotide position 71, causing the serine (S) at amino acid position 24 to be replaced by a cysteine (C). 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	0.098
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.5
DANN	Benign	0.92
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.33	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.092	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.54	N;.
REVEL	Benign	0.055
Sift	Uncertain	0.025	D;.
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.95	P;.
Vest4		0.19
MutPred		0.32		Loss of disorder (P = 0.0034);.;
MVP		0.39
ClinPred		0.16	T
GERP RS		0.034
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.060
gMVP		0.25

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: chr14-74036015;