17-42564502-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_025233.7(COASY):​c.972A>G​(p.Thr324Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 1,613,628 control chromosomes in the GnomAD database, including 243,335 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19201 hom., cov: 31)
Exomes 𝑓: 0.55 ( 224134 hom. )

Consequence

COASY
NM_025233.7 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.04
Variant links:
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 Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 17-42564502-A-G is Benign according to our data. Variant chr17-42564502-A-G is described in ClinVar as [Benign]. Clinvar id is 379957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-42564502-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-1.04 with no splicing effect.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COASYNM_025233.7 linkc.972A>G p.Thr324Thr synonymous_variant 3/9 ENST00000393818.3 NP_079509.5 Q13057-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COASYENST00000393818.3 linkc.972A>G p.Thr324Thr synonymous_variant 3/91 NM_025233.7 ENSP00000377406.1 Q13057-1

Frequencies

GnomAD3 genomes
AF:
0.499
AC:
75761
AN:
151796
Hom.:
19179
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.423
Gnomad AMI
AF:
0.465
Gnomad AMR
AF:
0.474
Gnomad ASJ
AF:
0.390
Gnomad EAS
AF:
0.438
Gnomad SAS
AF:
0.640
Gnomad FIN
AF:
0.530
Gnomad MID
AF:
0.408
Gnomad NFE
AF:
0.548
Gnomad OTH
AF:
0.474
GnomAD3 exomes
AF:
0.531
AC:
133422
AN:
251292
Hom.:
36076
AF XY:
0.537
AC XY:
72965
AN XY:
135832
show subpopulations
Gnomad AFR exome
AF:
0.416
Gnomad AMR exome
AF:
0.523
Gnomad ASJ exome
AF:
0.394
Gnomad EAS exome
AF:
0.440
Gnomad SAS exome
AF:
0.635
Gnomad FIN exome
AF:
0.533
Gnomad NFE exome
AF:
0.550
Gnomad OTH exome
AF:
0.499
GnomAD4 exome
AF:
0.551
AC:
805950
AN:
1461714
Hom.:
224134
Cov.:
53
AF XY:
0.553
AC XY:
402246
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.415
Gnomad4 AMR exome
AF:
0.522
Gnomad4 ASJ exome
AF:
0.391
Gnomad4 EAS exome
AF:
0.453
Gnomad4 SAS exome
AF:
0.632
Gnomad4 FIN exome
AF:
0.540
Gnomad4 NFE exome
AF:
0.560
Gnomad4 OTH exome
AF:
0.526
GnomAD4 genome
AF:
0.499
AC:
75814
AN:
151914
Hom.:
19201
Cov.:
31
AF XY:
0.498
AC XY:
36934
AN XY:
74238
show subpopulations
Gnomad4 AFR
AF:
0.422
Gnomad4 AMR
AF:
0.475
Gnomad4 ASJ
AF:
0.390
Gnomad4 EAS
AF:
0.438
Gnomad4 SAS
AF:
0.639
Gnomad4 FIN
AF:
0.530
Gnomad4 NFE
AF:
0.548
Gnomad4 OTH
AF:
0.478
Alfa
AF:
0.522
Hom.:
34096
Bravo
AF:
0.488
Asia WGS
AF:
0.572
AC:
1990
AN:
3478
EpiCase
AF:
0.523
EpiControl
AF:
0.517

ClinVar

Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:4
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, Amsterdam University Medical Center-- -
Benign, criteria provided, single submitterclinical testingUnidad de Genómica Garrahan, Hospital de Pediatría GarrahanJul 31, 2024This variant is classified as Benign based on local population frequency. This variant was detected in 75% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 70. Only high quality variants are reported. -
Benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, criteria provided, single submitterclinical testingGeneDxDec 02, 2015This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Neurodegeneration with brain iron accumulation 6 Benign:2
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 22, 2021- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 03, 2025- -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Pontocerebellar hypoplasia, type 12 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 22, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
1.3
DANN
Benign
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs598126; hg19: chr17-40716520; COSMIC: COSV55897798; COSMIC: COSV55897798; API