5-81335823-C-T

Position:

• chr5-81335823-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130767.3(ACOT12):​c.1207G>A​(p.Ala403Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,612,838 control chromosomes in the GnomAD database, including 19,691 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.15 (1806 hom., cov: 33)
  • Exomes 𝑓: 0.15 (17885 hom.)
• Consequence: ACOT12 NM_130767.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33

Genes affected

ACOT12 (HGNC:24436): (acyl-CoA thioesterase 12) Enables identical protein binding activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid metabolic process. Predicted to act upstream of or within acetyl-CoA metabolic process. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015539527).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACOT12	NM_130767.3	c.1207G>A	p.Ala403Thr	missense_variant	12/15	ENST00000307624.8	NP_570123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACOT12	ENST00000307624.8	c.1207G>A	p.Ala403Thr	missense_variant	12/15	1	NM_130767.3	ENSP00000303246	P1
ACOT12	ENST00000506440.1	n.80G>A		non_coding_transcript_exon_variant	1/3	2
ACOT12	ENST00000508234.5	n.187G>A		non_coding_transcript_exon_variant	3/6	3

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23139 AN: 152006 Hom.: 1803 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.163

GnomAD3 exomes AF: 0.131 AC: 32844 AN: 251092 Hom.: 2405 AF XY: 0.133 AC XY: 18012 AN XY: 135700

Gnomad AFR exome AF: 0.186

Gnomad AMR exome AF: 0.0887

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.00169

Gnomad SAS exome AF: 0.127

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.153 AC: 223445 AN: 1460714 Hom.: 17885 Cov.: 31 AF XY: 0.152 AC XY: 110582 AN XY: 726622

Gnomad4 AFR exome AF: 0.187

Gnomad4 AMR exome AF: 0.0918

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.00191

Gnomad4 SAS exome AF: 0.124

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.152 AC: 23163 AN: 152124 Hom.: 1806 Cov.: 33 AF XY: 0.149 AC XY: 11109 AN XY: 74376

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.00425

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.160

Alfa AF: 0.159 Hom.: 2205

Bravo AF: 0.155

TwinsUK AF: 0.170 AC: 630

ALSPAC AF: 0.164 AC: 631

ESP6500AA AF: 0.193 AC: 849

ESP6500EA AF: 0.156 AC: 1345

ExAC AF: 0.136 AC: 16498

Asia WGS AF: 0.0760 AC: 266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.088	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	0.99	P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.028
Sift	Benign	0.17	T
Sift4G	Benign	0.24	T
Polyphen		0.051	B
Vest4		0.077
MPC		0.10
ClinPred		0.010	T
GERP RS		4.3
Varity_R		0.037
gMVP		0.28

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: rs10371; hg19: chr5-80631642;