17-42564502-A-G

Position:

chr17-42564502-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

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]

COASY links:

Genome browser will be placed here

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
COASY	NM_025233.7 link	c.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
COASY	ENST00000393818.3 link	c.972A>G	p.Thr324Thr	synonymous_variant	3/9	1	NM_025233.7	ENSP00000377406.1		Q13057-1

Frequencies

GnomAD3 genomes

AF:

0.499

AC:

75761

AN:

151796

Hom.:

19179

Cov.:

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.:

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.:

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 provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 31, 2024	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. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2015	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. -

Neurodegeneration with brain iron accumulation 6

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Pontocerebellar hypoplasia, type 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over