15-75043523-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001301104.2(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 NM_001301104.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.47

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 Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPCDC	NM_021823.5	c.218C>A	p.Ala73Asp	missense_variant	Exon 3 of 6	ENST00000342932.8	NP_068595.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPCDC	ENST00000342932.8	c.218C>A	p.Ala73Asp	missense_variant	Exon 3 of 6	1	NM_021823.5	ENSP00000343190.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.218C>A (p.A73D) alteration is located in exon 3 (coding exon 2) of the PPCDC gene. This alteration results from a C to A substitution at nucleotide position 218, causing the alanine (A) at amino acid position 73 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.037
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.10	N;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.46	N;N
REVEL	Benign	0.051
Sift	Benign	0.60	T;T
Sift4G	Benign	0.42	T;T
Polyphen		0.0	B;.
Vest4		0.48
MutPred		0.49		Gain of disorder (P = 0.046);Gain of disorder (P = 0.046);
MVP		0.63
MPC		0.17
ClinPred		0.67	D
GERP RS		5.5
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-75335864;