rs878858402

Variant names:

• chr14-73569262-C-G
• rs878858402
• NM_006821.6:c.22C>G

Variant summary

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

The NM_001364177.1(ACOT2):​c.-83C>G variant causes a 5 prime UTR premature start codon gain 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACOT2 NM_001364177.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0790
• Publications: 1 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054252654).

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.22C>G	p.Pro8Ala	missense	Exon 1 of 3	NP_006812.3
	ACOT2	NM_001364177.1		c.-83C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001351106.1	B3KSA0
	ACOT2	NM_001364178.1		c.22C>G	p.Pro8Ala	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.22C>G	p.Pro8Ala	missense	Exon 1 of 3	ENSP00000238651.5	P49753-1
	ACOT2	ENST00000864002.1		c.22C>G	p.Pro8Ala	missense	Exon 1 of 3	ENSP00000534061.1
	ACOT2	ENST00000913953.1		c.22C>G	p.Pro8Ala	missense	Exon 1 of 2	ENSP00000584012.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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	0.060
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.0
DANN	Benign	0.58
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.079
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.020
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.27	T
Polyphen		0.0020	B
Vest4		0.22
MutPred		0.20		Loss of stability (P = 0.0323)
MVP		0.11
ClinPred		0.040	T
GERP RS		-1.4
PromoterAI		-0.53	Under-expression
Varity_R		0.042
gMVP		0.15
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

dbSNP: rs878858402; hg19: chr14-74035966;