rs753858819

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr14-73592012-C-G
• chr14-73592012-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACOT4	NM_152331.4	c.53C>G	p.Pro18Arg	missense_variant	Exon 1 of 3	ENST00000326303.5	NP_689544.3
HEATR4	XM_047431370.1	c.-73+41649G>C		intron_variant	Intron 1 of 16		XP_047287326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACOT4	ENST00000326303.5	c.53C>G	p.Pro18Arg	missense_variant	Exon 1 of 3	1	NM_152331.4	ENSP00000323071.4
ENSG00000258603	ENST00000664243.1	n.63-34040G>C		intron_variant	Intron 1 of 1
ENSG00000288797	ENST00000686335.1	n.-127C>G		upstream_gene_variant

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

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: 0.00000389

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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
Varity_R		0.80
gMVP		0.60

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: chr14-74058716;