chr5-81335781-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_130767.3(ACOT12):​c.1249G>T​(p.Asp417Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ACOT12
NM_130767.3 missense

Scores

7
8
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.68
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.922

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACOT12NM_130767.3 linkc.1249G>T p.Asp417Tyr missense_variant Exon 12 of 15 ENST00000307624.8 NP_570123.1 Q8WYK0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACOT12ENST00000307624.8 linkc.1249G>T p.Asp417Tyr missense_variant Exon 12 of 15 1 NM_130767.3 ENSP00000303246.3 Q8WYK0-1
ACOT12ENST00000506440.1 linkn.122G>T non_coding_transcript_exon_variant Exon 1 of 3 2
ACOT12ENST00000508234.5 linkn.229G>T non_coding_transcript_exon_variant Exon 3 of 6 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 15, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1249G>T (p.D417Y) alteration is located in exon 12 (coding exon 12) of the ACOT12 gene. This alteration results from a G to T substitution at nucleotide position 1249, causing the aspartic acid (D) at amino acid position 417 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.82
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.090
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.58
D
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.074
D
MetaRNN
Pathogenic
0.92
D
MetaSVM
Benign
-0.37
T
MutationAssessor
Pathogenic
3.3
M
PrimateAI
Uncertain
0.49
T
PROVEAN
Pathogenic
-6.2
D
REVEL
Uncertain
0.50
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.95
MutPred
0.67
Loss of ubiquitination at K412 (P = 0.0716);
MVP
0.67
MPC
0.54
ClinPred
0.99
D
GERP RS
5.1
Varity_R
0.82
gMVP
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.17
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-80631600; API