15-75028448-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021823.5(PPCDC):​c.130C>T​(p.Pro44Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,614,082 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

PPCDC
NM_021823.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.15484434).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPCDCNM_021823.5 linkc.130C>T p.Pro44Ser missense_variant Exon 2 of 6 ENST00000342932.8 NP_068595.3 Q96CD2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPCDCENST00000342932.8 linkc.130C>T p.Pro44Ser missense_variant Exon 2 of 6 1 NM_021823.5 ENSP00000343190.3 Q96CD2-1

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000636
AC:
16
AN:
251422
Hom.:
0
AF XY:
0.0000662
AC XY:
9
AN XY:
135906
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000132
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000149
AC:
218
AN:
1461870
Hom.:
1
Cov.:
31
AF XY:
0.000139
AC XY:
101
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000189
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152212
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000453
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.000228
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000741
AC:
9
EpiCase
AF:
0.000218
EpiControl
AF:
0.000178

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.130C>T (p.P44S) alteration is located in exon 2 (coding exon 1) of the PPCDC gene. This alteration results from a C to T substitution at nucleotide position 130, causing the proline (P) at amino acid position 44 to be replaced by a serine (S). 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
0.11
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
T;.;T;T;.
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.11
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.78
T;T;T;T;T
M_CAP
Benign
0.0070
T
MetaRNN
Benign
0.15
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
L;.;.;.;.
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-1.5
N;N;N;N;N
REVEL
Benign
0.15
Sift
Benign
0.26
T;D;T;T;T
Sift4G
Benign
0.66
T;T;T;T;T
Polyphen
0.011
B;.;.;.;.
Vest4
0.21
MVP
0.74
MPC
0.11
ClinPred
0.10
T
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.23
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs147547634; hg19: chr15-75320789; API