14-73592110-C-G

Variant names:

• chr14-73592110-C-G
• rs1199364877
• NM_152331.4:c.151C>G

Variant summary

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

The NM_152331.4(ACOT4):​c.151C>G​(p.Arg51Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,357,698 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. R51S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: ACOT4 NM_152331.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• 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.151C>G	p.Arg51Gly	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.151C>G	p.Arg51Gly	missense	Exon 1 of 3	ENSP00000323071.4	Q8N9L9
	ENSG00000258603	ENST00000664243.1		n.63-34138G>C		intron	N/A
	ENSG00000258603	ENST00000761264.1		n.186+41551G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.37e-7 AC: 1 AN: 1357698 Hom.: 0 Cov.: 29 AF XY: 0.00000149 AC XY: 1 AN XY: 669128

African (AFR) AF: 0.00 AC: 0 AN: 26848

American (AMR) AF: 0.00 AC: 0 AN: 28312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22590

East Asian (EAS) AF: 0.0000307 AC: 1 AN: 32596

South Asian (SAS) AF: 0.00 AC: 0 AN: 73688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48024

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5204

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1064578

Other (OTH) AF: 0.00 AC: 0 AN: 55858

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	27
DANN	Uncertain	0.97
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.024
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.28	N
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		0.016
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.47
Sift	Benign	0.10	T
Sift4G	Benign	0.33	T
Polyphen		1.0	D
Vest4		0.46
MutPred		0.57		Gain of catalytic residue at F46 (P = 0)
MVP		0.76
MPC		1.0
ClinPred		0.85	D
GERP RS		4.0
PromoterAI		-0.12	Neutral
Varity_R		0.95
gMVP		0.72
Mutation Taster		=69/31	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: rs1199364877; hg19: chr14-74058814;