rs615942

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025233.7(COASY):c.164C>A(p.Ser55Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.547 in 1,609,410 control chromosomes in the GnomAD database, including 243,392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19459 hom., cov: 32)

Exomes 𝑓: 0.55 ( 223933 hom. )

Consequence

COASY
NM_025233.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.22

Publications

56 publications found

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]

COASY Gene-Disease associations (from GenCC):

neurodegeneration with brain iron accumulation 6
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, G2P, Orphanet
pontocerebellar hypoplasia, type 12
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

COASY links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.2346416E-5).

BP6

Variant 17-42562786-C-A is Benign according to our data. Variant chr17-42562786-C-A is described in ClinVar as Benign. ClinVar VariationId is 379956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
COASY	NM_025233.7 link	c.164C>A	p.Ser55Tyr	missense_variant	Exon 1 of 9	ENST00000393818.3	NP_079509.5	Q13057-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COASY	ENST00000393818.3 link	c.164C>A	p.Ser55Tyr	missense_variant	Exon 1 of 9	1	NM_025233.7	ENSP00000377406.1		Q13057-1

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76366

AN:

151876

Hom.:

19437

Cov.:

show subpopulations

Gnomad AFR

AF:

0.435

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.391

Gnomad EAS

AF:

0.437

Gnomad SAS

AF:

0.640

Gnomad FIN

AF:

0.531

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.549

Gnomad OTH

AF:

0.476

GnomAD2 exomes

AF:

0.532

AC:

132584

AN:

249248

AF XY:

0.538

show subpopulations

Gnomad AFR exome

AF:

0.427

Gnomad AMR exome

AF:

0.523

Gnomad ASJ exome

AF:

0.394

Gnomad EAS exome

AF:

0.440

Gnomad FIN exome

AF:

0.533

Gnomad NFE exome

AF:

0.550

Gnomad OTH exome

AF:

0.501

GnomAD4 exome

AF:

0.552

AC:

804458

AN:

1457416

Hom.:

223933

Cov.:

AF XY:

0.554

AC XY:

401155

AN XY:

724372

show subpopulations

African (AFR)

AF:

0.426

AC:

14231

AN:

33414

American (AMR)

AF:

0.522

AC:

23290

AN:

44628

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

10214

AN:

26082

East Asian (EAS)

AF:

0.453

AC:

17929

AN:

39596

South Asian (SAS)

AF:

0.632

AC:

54460

AN:

86140

European-Finnish (FIN)

AF:

0.540

AC:

28189

AN:

52180

Middle Eastern (MID)

AF:

0.409

AC:

2356

AN:

5760

European-Non Finnish (NFE)

AF:

0.561

AC:

622068

AN:

1109454

Other (OTH)

AF:

0.527

AC:

31721

AN:

60162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

22539

45077

67616

90154

112693

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17450

34900

52350

69800

87250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.503

AC:

76421

AN:

151994

Hom.:

19459

Cov.:

AF XY:

0.501

AC XY:

37210

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.435

AC:

18025

AN:

41444

American (AMR)

AF:

0.475

AC:

7264

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.391

AC:

1355

AN:

3468

East Asian (EAS)

AF:

0.437

AC:

2256

AN:

5166

South Asian (SAS)

AF:

0.639

AC:

3078

AN:

4818

European-Finnish (FIN)

AF:

0.531

AC:

5617

AN:

10576

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.549

AC:

37273

AN:

67924

Other (OTH)

AF:

0.480

AC:

1012

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1974

3948

5923

7897

9871

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

696

1392

2088

2784

3480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.528

Hom.:

67439

Bravo

AF:

0.491

TwinsUK

AF:

0.564

AC:

2093

ALSPAC

AF:

0.567

AC:

2186

ESP6500AA

AF:

0.431

AC:

1897

ESP6500EA

AF:

0.543

AC:

4667

ExAC

AF:

0.536

AC:

65057

Asia WGS

AF:

0.572

AC:

1992

AN:

3478

EpiCase

AF:

0.523

EpiControl

AF:

0.518

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 31, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This 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. -

Dec 02, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This 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. -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Neurodegeneration with brain iron accumulation 6

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pontocerebellar hypoplasia, type 12

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

.;T;T;T;.;T;.;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.51

T;T;T;.;T;T;T;T

MetaRNN

Benign

0.000032

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.90

.;.;.;L;.;.;.;L

PhyloP100

5.2

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.88

.;.;.;.;.;.;.;N

REVEL

Benign

0.064

Sift

Benign

0.089

.;.;.;.;.;.;.;T

Sift4G

Uncertain

0.034

D;D;D;D;D;D;D;D

Polyphen

0.80, 0.94

.;.;.;P;.;.;P;P

Vest4

0.18, 0.10, 0.19

MPC

0.78

ClinPred

0.021

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.27

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over