rs772051643

Variant names:

• chr5-81335792-C-G
• rs772051643
• NM_130767.3:c.1238G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-81335792-C-G
• chr5-81335792-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_130767.3(ACOT12):​c.1238G>C​(p.Arg413Pro) 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. R413Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACOT12 NM_130767.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.888

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130767.3. 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
	ACOT12	NM_130767.3	MANE Select	c.1238G>C	p.Arg413Pro	missense	Exon 12 of 15	NP_570123.1	Q8WYK0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOT12	ENST00000307624.8	TSL:1 MANE Select	c.1238G>C	p.Arg413Pro	missense	Exon 12 of 15	ENSP00000303246.3	Q8WYK0-1
	ACOT12	ENST00000905739.1		c.1136G>C	p.Arg379Pro	missense	Exon 11 of 14	ENSP00000575798.1
	ACOT12	ENST00000905740.1		c.1238G>C	p.Arg413Pro	missense	Exon 12 of 14	ENSP00000575799.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.056	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-0.44	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		3.2
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.69		Gain of catalytic residue at R413 (P = 0.0103)
MVP		0.57
MPC		0.58
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.84
gMVP		0.90
Mutation Taster		=34/66	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs772051643; hg19: chr5-80631611;