17-42562662-C-T
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_025233.7(COASY):c.40C>T(p.Pro14Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000146 in 1,371,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000015 ( 0 hom. )
Consequence
COASY
NM_025233.7 missense
NM_025233.7 missense
Scores
4
10
5
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.15
Genes affected
COASY (HGNC:29932): (Coenzyme A synthase) Coenzyme A (CoA) functions as a carrier of acetyl and acyl groups in cells and thus plays an important role in numerous synthetic and degradative metabolic pathways in all organisms. In eukaryotes, CoA and its derivatives are also involved in membrane trafficking and signal transduction. This gene encodes the bifunctional protein coenzyme A synthase (CoAsy) which carries out the last two steps in the biosynthesis of CoA from pantothenic acid (vitamin B5). The phosphopantetheine adenylyltransferase domain of this bifunctional protein catalyzes the conversion of 4'-phosphopantetheine into dephospho-coenzyme A (dpCoA) while its dephospho-CoA kinase domain completes the final step by phosphorylating dpCoA to form CoA. Mutations in this gene are associated with neurodegeneration with brain iron accumulation (NBIA). Alternative splicing results in multiple isoforms. [provided by RefSeq, Apr 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.766
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000146 AC: 2AN: 1371174Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 673740
GnomAD4 exome
AF:
AC:
2
AN:
1371174
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
673740
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 NFE exome
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Gnomad4 OTH exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
.;T;T;T;.;T;.;T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;T;.;D;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;.;L;.;.;.;L
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;.;.;.;.;.;.;D
REVEL
Uncertain
Sift
Uncertain
.;.;.;.;.;.;.;D
Sift4G
Pathogenic
D;D;D;D;D;D;D;D
Polyphen
1.0, 1.0
.;.;.;D;.;.;D;D
Vest4
0.68, 0.67, 0.68
MutPred
Gain of catalytic residue at P14 (P = 0.0071);.;Gain of catalytic residue at P14 (P = 0.0071);Gain of catalytic residue at P14 (P = 0.0071);.;Gain of catalytic residue at P14 (P = 0.0071);.;Gain of catalytic residue at P14 (P = 0.0071);
MVP
MPC
0.87
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.