chr14-73592012-C-G

Variant names:

• chr14-73592012-C-G
• rs753858819
• NM_152331.4:c.53C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152331.4(ACOT4):​c.53C>G​(p.Pro18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000312 in 1,281,544 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P18L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: ACOT4 NM_152331.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• Publications: 0 publications found

Genes affected

ACOT4 (HGNC:19748): (acyl-CoA thioesterase 4) Enables acyl-CoA hydrolase activity and succinyl-CoA hydrolase activity. Involved in carboxylic acid metabolic process; saturated monocarboxylic acid metabolic process; and succinyl-CoA metabolic process. Located in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152331.4. 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
	ACOT4	NM_152331.4	MANE Select	c.53C>G	p.Pro18Arg	missense	Exon 1 of 3	NP_689544.3	Q8N9L9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOT4	ENST00000326303.5	TSL:1 MANE Select	c.53C>G	p.Pro18Arg	missense	Exon 1 of 3	ENSP00000323071.4	Q8N9L9
	ENSG00000258603	ENST00000664243.1		n.63-34040G>C		intron	N/A
	ENSG00000258603	ENST00000761264.1		n.186+41649G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000312 AC: 4 AN: 1281544 Hom.: 0 Cov.: 29 AF XY: 0.00000478 AC XY: 3 AN XY: 627318

African (AFR) AF: 0.00 AC: 0 AN: 24658

American (AMR) AF: 0.00 AC: 0 AN: 15046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20032

East Asian (EAS) AF: 0.00 AC: 0 AN: 28510

South Asian (SAS) AF: 0.00 AC: 0 AN: 63006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4280

European-Non Finnish (NFE) AF: 0.00000389 AC: 4 AN: 1028144

Other (OTH) AF: 0.00 AC: 0 AN: 52496

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.55	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	0.25	D
MutationAssessor	Pathogenic	3.5	M
PhyloP100		1.7
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-8.2	D
REVEL	Uncertain	0.46
Sift	Benign	0.039	D
Sift4G	Uncertain	0.055	T
Polyphen		0.90	P
Vest4		0.39
MutPred		0.64		Gain of catalytic residue at W15 (P = 0)
MVP		0.78
MPC		0.94
ClinPred		0.99	D
GERP RS		4.8
PromoterAI		-0.019	Neutral
Varity_R		0.80
gMVP		0.60
Mutation Taster		=93/7	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: rs753858819; hg19: chr14-74058716;