rs35724886

chr14-73593804-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152331.4(ACOT4):c.560C>A(p.Ala187Asp) variant causes a missense change. The variant allele was found at a frequency of 0.186 in 1,607,944 control chromosomes in the GnomAD database, including 32,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.15 (2210 hom., cov: 32)
  • Exomes 𝑓: 0.19 (29806 hom.)
• Consequence: ACOT4 NM_152331.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.17

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026230812).
• BP6: Variant 14-73593804-C-A is Benign according to our data. Variant chr14-73593804-C-A is described in ClinVar as [Benign]. Clinvar id is 2798877.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACOT4	NM_152331.4	c.560C>A	p.Ala187Asp	missense_variant	2/3	ENST00000326303.5
HEATR4	XM_047431370.1	c.-73+39857G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACOT4	ENST00000326303.5	c.560C>A	p.Ala187Asp	missense_variant	2/3	1	NM_152331.4	P1
	ENST00000664243.1	n.63-35832G>T		intron_variant, non_coding_transcript_variant
	ENST00000686335.1	n.279-1245C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22370 AN: 152052 Hom.: 2209 Cov.: 32

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0652

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.136

GnomAD3 exomes AF: 0.0495 AC: 10293 AN: 207986 Hom.: 1840 AF XY: 0.0491 AC XY: 5490 AN XY: 111854

Gnomad AFR exome AF: 0.0110

Gnomad AMR exome AF: 0.0153

Gnomad ASJ exome AF: 0.0319

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0172

Gnomad FIN exome AF: 0.142

Gnomad NFE exome AF: 0.0743

Gnomad OTH exome AF: 0.0452

GnomAD4 exome AF: 0.190 AC: 277149 AN: 1455774 Hom.: 29806 Cov.: 32 AF XY: 0.186 AC XY: 134915 AN XY: 723760

Gnomad4 AFR exome AF: 0.0453

Gnomad4 AMR exome AF: 0.0867

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.000504

Gnomad4 SAS exome AF: 0.0723

Gnomad4 FIN exome AF: 0.253

Gnomad4 NFE exome AF: 0.216

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.147 AC: 22371 AN: 152170 Hom.: 2210 Cov.: 32 AF XY: 0.145 AC XY: 10827 AN XY: 74416

Gnomad4 AFR AF: 0.0523

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.0654

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.134

Alfa AF: 0.0376 Hom.: 770

Bravo AF: 0.133

ESP6500AA AF: 0.0172 AC: 76

ESP6500EA AF: 0.0974 AC: 837

ExAC AF: 0.128 AC: 15546

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.29
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Pathogenic	3.7	H
MutationTaster	Benign	2.9e-9	P
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0060	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.34
MPC		1.1
ClinPred		0.074	T
GERP RS		5.3
Varity_R		0.95
gMVP		0.95

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

LitVar

Other links and lift over

dbSNP: rs35724886; hg19: chr14-74060508;