Genetic Variant PPCDC:c.-72-155G>T (chr15-75028092-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021823.5(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
NM_021823.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0250

Publications

16 publications found

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]

PPCDC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021823.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPCDC	NM_021823.5	MANE Select	c.-72-155G>T	intron	N/A	NP_068595.3
PPCDC	NM_001301102.2		c.-72-155G>T	intron	N/A	NP_001288031.1	H3BRQ0
PPCDC	NM_001301101.2		c.-72-155G>T	intron	N/A	NP_001288030.1	H3BQB0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPCDC	ENST00000342932.8	TSL:1 MANE Select	c.-72-155G>T	intron	N/A	ENSP00000343190.3	Q96CD2-1
PPCDC	ENST00000889947.1		c.-47-180G>T	intron	N/A	ENSP00000560006.1
PPCDC	ENST00000889948.1		c.-72-155G>T	intron	N/A	ENSP00000560007.1

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57628

AN:

151870

Hom.:

12370

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.527

AC:

5936

AN:

11264

American (AMR)

AF:

0.412

AC:

6231

AN:

15126

Ashkenazi Jewish (ASJ)

AF:

0.404

AC:

4920

AN:

12178

East Asian (EAS)

AF:

0.596

AC:

15313

AN:

25686

South Asian (SAS)

AF:

0.648

AC:

24535

AN:

37852

European-Finnish (FIN)

AF:

0.258

AC:

6580

AN:

25458

Middle Eastern (MID)

AF:

0.494

AC:

866

AN:

1752

European-Non Finnish (NFE)

AF:

0.260

AC:

64118

AN:

246336

Other (OTH)

AF:

0.358

AC:

8236

AN:

23014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

3830

7660

11489

15319

19149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

628

1256

1884

2512

3140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.380

AC:

57692

AN:

151988

Hom.:

12388

Cov.:

AF XY:

0.388

AC XY:

28818

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.528

AC:

21901

AN:

41446

American (AMR)

AF:

0.388

AC:

5923

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

1371

AN:

3468

East Asian (EAS)

AF:

0.663

AC:

3422

AN:

5160

South Asian (SAS)

AF:

0.658

AC:

3168

AN:

4812

European-Finnish (FIN)

AF:

0.273

AC:

2883

AN:

10566

Middle Eastern (MID)

AF:

0.490

AC:

144

AN:

294

European-Non Finnish (NFE)

AF:

0.261

AC:

17750

AN:

67956

Other (OTH)

AF:

0.403

AC:

849

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1692

3384

5075

6767

8459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.318

Hom.:

12228

Bravo

AF:

0.388

Asia WGS

AF:

0.669

AC:

2322

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.1

(source)

DANN

Benign

0.44

PhyloP100

0.025

PromoterAI

0.060

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over