chr15-75041843-T-C

Variant names:

• chr15-75041843-T-C
• rs2120019
• NM_021823.5:c.136-1598T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021823.5(PPCDC):​c.136-1598T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,986 control chromosomes in the GnomAD database, including 8,844 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 0.32 (8844 hom., cov: 32)
• Consequence: PPCDC NM_021823.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPCDC	NM_021823.5	c.136-1598T>C		intron_variant	Intron 2 of 5	ENST00000342932.8	NP_068595.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPCDC	ENST00000342932.8	c.136-1598T>C		intron_variant	Intron 2 of 5	1	NM_021823.5	ENSP00000343190.3

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47926 AN: 151868 Hom.: 8828 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.350

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.316 AC: 47988 AN: 151986 Hom.: 8844 Cov.: 32 AF XY: 0.323 AC XY: 23994 AN XY: 74298

African (AFR) AF: 0.459 AC: 19020 AN: 41418

American (AMR) AF: 0.274 AC: 4185 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1129 AN: 3470

East Asian (EAS) AF: 0.597 AC: 3083 AN: 5168

South Asian (SAS) AF: 0.589 AC: 2838 AN: 4822

European-Finnish (FIN) AF: 0.218 AC: 2302 AN: 10576

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.211 AC: 14321 AN: 67960

Other (OTH) AF: 0.349 AC: 733 AN: 2102

Alfa AF: 0.262 Hom.: 9983

Bravo AF: 0.319

Asia WGS AF: 0.602 AC: 2089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.5
DANN	Benign	0.36
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2120019; hg19: chr15-75334184; COSMIC: COSV61625493; COSMIC: COSV61625493;