chr15-75028092-G-T

Position:

• chr15-75028092-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000342932.8(PPCDC):​c.-72-155G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 550,654 control chromosomes in the GnomAD database, including 40,483 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.38 (12388 hom., cov: 32)
  • Exomes 𝑓: 0.34 (28095 hom.)
• Consequence: PPCDC ENST00000342932.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250

Genes affected

PPCDC (HGNC:28107): (phosphopantothenoylcysteine decarboxylase) Biosynthesis of coenzyme A (CoA) from pantothenic acid (vitamin B5) is an essential universal pathway in prokaryotes and eukaryotes. PPCDC (EC 4.1.1.36), one of the last enzymes in this pathway, converts phosphopantothenoylcysteine to 4-prime-phosphopantetheine (Daugherty et al., 2002 [PubMed 11923312]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPCDC	NM_021823.5	c.-72-155G>T		intron_variant		ENST00000342932.8	NP_068595.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPCDC	ENST00000342932.8	c.-72-155G>T		intron_variant		1	NM_021823.5	ENSP00000343190	P1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57628 AN: 151870 Hom.: 12370 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.343 AC: 136735 AN: 398666 Hom.: 28095 AF XY: 0.358 AC XY: 74689 AN XY: 208416

Gnomad4 AFR exome AF: 0.527

Gnomad4 AMR exome AF: 0.412

Gnomad4 ASJ exome AF: 0.404

Gnomad4 EAS exome AF: 0.596

Gnomad4 SAS exome AF: 0.648

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.358

GnomAD4 genome AF: 0.380 AC: 57692 AN: 151988 Hom.: 12388 Cov.: 32 AF XY: 0.388 AC XY: 28818 AN XY: 74268

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.663

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.403

Alfa AF: 0.302 Hom.: 7317

Bravo AF: 0.388

Asia WGS AF: 0.669 AC: 2322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.44

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

LitVar

Other links and lift over

dbSNP: rs8042558; hg19: chr15-75320433;