17-42561996-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000588757.1(COASY):n.301C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 178,412 control chromosomes in the GnomAD database, including 28,219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (24405 hom., cov: 33)
  • Exomes 𝑓: 0.52 (3814 hom.)
• Consequence: COASY ENST00000588757.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.73

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-42561996-C-A is Benign according to our data. Variant chr17-42561996-C-A is described in ClinVar as [Benign]. Clinvar id is 1263643.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COASY	ENST00000588757.1	n.301C>A		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85610 AN: 151924 Hom.: 24379 Cov.: 33

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.512

GnomAD4 exome AF: 0.522 AC: 13762 AN: 26370 Hom.: 3814 Cov.: 0 AF XY: 0.525 AC XY: 7312 AN XY: 13928

Gnomad4 AFR exome AF: 0.630

Gnomad4 AMR exome AF: 0.520

Gnomad4 ASJ exome AF: 0.329

Gnomad4 EAS exome AF: 0.452

Gnomad4 SAS exome AF: 0.609

Gnomad4 FIN exome AF: 0.516

Gnomad4 NFE exome AF: 0.526

Gnomad4 OTH exome AF: 0.490

GnomAD4 genome AF: 0.564 AC: 85685 AN: 152042 Hom.: 24405 Cov.: 33 AF XY: 0.559 AC XY: 41581 AN XY: 74324

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.516

Alfa AF: 0.403 Hom.: 1063

Bravo AF: 0.562

Asia WGS AF: 0.594 AC: 2067 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.025
Dann	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs629861; hg19: chr17-40714014;