ENST00000563393.1:c.-152C>A

Variant names:

• chr15-75043523-C-A
• ENST00000563393.1:c.-152C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000563393.1(PPCDC):​c.-152C>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PPCDC ENST00000563393.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.47
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18493718).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000563393.1. 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
	PPCDC	NM_021823.5	MANE Select	c.218C>A	p.Ala73Asp	missense	Exon 3 of 6	NP_068595.3
	PPCDC	NM_001301104.2		c.-152C>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	NP_001288033.1	H3BU63
	PPCDC	NM_001301105.2		c.-152C>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	NP_001288034.1	H3BU63

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPCDC	ENST00000563393.1	TSL:1	c.-152C>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000457490.1	H3BU63
	PPCDC	ENST00000342932.8	TSL:1 MANE Select	c.218C>A	p.Ala73Asp	missense	Exon 3 of 6	ENSP00000343190.3	Q96CD2-1
	PPCDC	ENST00000563393.1	TSL:1	c.-152C>A		5_prime_UTR	Exon 1 of 4	ENSP00000457490.1	H3BU63

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Benign	0.86
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.037
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.10	N
PhyloP100		3.5
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.051
Sift	Benign	0.60	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.48
MutPred		0.49		Gain of disorder (P = 0.046)
MVP		0.63
MPC		0.17
ClinPred		0.67	D
GERP RS		5.5
PromoterAI		0.0026	Neutral
Varity_R		0.38
gMVP		0.66

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

hg19: chr15-75335864;