17-42561996-C-A

Variant names:

• chr17-42561996-C-A
• rs629861
• ENST00000585572.1:n.528C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000585572.1(ENSG00000266929):​n.528C>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: ENSG00000266929 ENST00000585572.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.73
• Publications: 14 publications found

Genes affected

ENSG00000266929 (HGNC:):

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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• pontocerebellar hypoplasia, type 12

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1263643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000585572.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COASY	NM_025233.7	MANE Select	c.-627C>A		upstream_gene	N/A	NP_079509.5
	COASY	NM_001042532.4		c.-280C>A		upstream_gene	N/A	NP_001035997.2	Q13057-2
	COASY	NM_001042529.3		c.-235C>A		upstream_gene	N/A	NP_001035994.1	Q13057-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000266929	ENST00000585572.1	TSL:4	n.528C>A		non_coding_transcript_exon	Exon 5 of 5
	COASY	ENST00000588757.1	TSL:4	n.301C>A		non_coding_transcript_exon	Exon 2 of 2
	COASY	ENST00000393818.3	TSL:1 MANE Select	c.-627C>A		upstream_gene	N/A	ENSP00000377406.1	Q13057-1

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

African (AFR) AF: 0.630 AC: 595 AN: 944

American (AMR) AF: 0.520 AC: 393 AN: 756

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 319 AN: 970

East Asian (EAS) AF: 0.452 AC: 582 AN: 1288

South Asian (SAS) AF: 0.609 AC: 1314 AN: 2158

European-Finnish (FIN) AF: 0.516 AC: 659 AN: 1278

Middle Eastern (MID) AF: 0.389 AC: 42 AN: 108

European-Non Finnish (NFE) AF: 0.526 AC: 9044 AN: 17208

Other (OTH) AF: 0.490 AC: 814 AN: 1660

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

African (AFR) AF: 0.648 AC: 26863 AN: 41462

American (AMR) AF: 0.496 AC: 7579 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1356 AN: 3472

East Asian (EAS) AF: 0.439 AC: 2269 AN: 5172

South Asian (SAS) AF: 0.641 AC: 3089 AN: 4820

European-Finnish (FIN) AF: 0.529 AC: 5591 AN: 10578

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37303 AN: 67952

Other (OTH) AF: 0.516 AC: 1092 AN: 2116

Alfa AF: 0.423 Hom.: 1226

Bravo AF: 0.562

Asia WGS AF: 0.594 AC: 2067 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.025
DANN	Benign	0.51
PhyloP100		-3.7
PromoterAI		0.00010	Neutral

Splicing

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

Other links and lift over

dbSNP: rs629861; hg19: chr17-40714014;