chr14-73592007-C-A

Variant names:

• chr14-73592007-C-A
• rs573072624
• NM_152331.4:c.48C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152331.4(ACOT4):​c.48C>A​(p.Asn16Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000157 in 1,277,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: ACOT4 NM_152331.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20828462).

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.48C>A	p.Asn16Lys	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.48C>A	p.Asn16Lys	missense	Exon 1 of 3	ENSP00000323071.4	Q8N9L9
	ENSG00000258603	ENST00000664243.1		n.63-34035G>T		intron	N/A
	ENSG00000258603	ENST00000761264.1		n.186+41654G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000157 AC: 2 AN: 1277282 Hom.: 0 Cov.: 29 AF XY: 0.00000320 AC XY: 2 AN XY: 624774

African (AFR) AF: 0.00 AC: 0 AN: 24588

American (AMR) AF: 0.00 AC: 0 AN: 14528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19800

East Asian (EAS) AF: 0.00 AC: 0 AN: 28402

South Asian (SAS) AF: 0.00 AC: 0 AN: 62092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4254

European-Non Finnish (NFE) AF: 0.00000195 AC: 2 AN: 1026110

Other (OTH) AF: 0.00 AC: 0 AN: 52338

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Benign	0.050
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.49	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.0020
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.79	P
Vest4		0.27
MutPred		0.68		Gain of catalytic residue at W15 (P = 0)
MVP		0.72
MPC		0.30
ClinPred		0.79	D
GERP RS		3.9
PromoterAI		-0.015	Neutral
Varity_R		0.70
gMVP		0.67
Mutation Taster		=86/14	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: rs573072624; hg19: chr14-74058711;