rs139322329

Variant names:

• chr14-73593798-C-A
• rs139322329
• NM_152331.4:c.554C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-73593798-C-A
• chr14-73593798-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152331.4(ACOT4):​c.554C>A​(p.Thr185Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. T185M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ACOT4 NM_152331.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398
• Publications: 1 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.79

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.554C>A	p.Thr185Lys	missense	Exon 2 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.554C>A	p.Thr185Lys	missense	Exon 2 of 3	ENSP00000323071.4	Q8N9L9
	ENSG00000258603	ENST00000664243.1		n.63-35826G>T		intron	N/A
	ENSG00000288797	ENST00000686335.1		n.279-1251C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000228 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.071
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		-0.40
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.037	D
Polyphen		0.99	D
Vest4		0.78
MutPred		0.59		Gain of catalytic residue at G180 (P = 0)
MVP		0.63
MPC		0.63
ClinPred		0.98	D
GERP RS		2.2
Varity_R		0.79
gMVP		0.84
Mutation Taster		=89/11	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: rs139322329; hg19: chr14-74060502;