chr14-73569311-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09164551).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364177.1. 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.71C>G	p.Ser24Cys	missense	Exon 1 of 3	NP_006812.3
	ACOT2	NM_001364177.1		c.-34C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001351106.1	B3KSA0
	ACOT2	NM_001364178.1		c.71C>G	p.Ser24Cys	missense	Exon 1 of 3	NP_001351107.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOT2	ENST00000238651.10	TSL:1 MANE Select	c.71C>G	p.Ser24Cys	missense	Exon 1 of 3	ENSP00000238651.5	P49753-1
	ACOT2	ENST00000613168.1	TSL:1	c.11C>G	p.Ser4Cys	missense	Exon 1 of 3	ENSP00000477685.1	A0A087WT95
	ACOT2	ENST00000864002.1		c.71C>G	p.Ser24Cys	missense	Exon 1 of 3	ENSP00000534061.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111802

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 33

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	0.098
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
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		-1.4
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.055
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.0060	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
PromoterAI		-0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.060
gMVP		0.25
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

hg19: chr14-74036015;