Variant chr15-75044388-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001301104.2(PPCDC):c.-136A>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.924 in 1,613,604 control chromosomes in the GnomAD database, including 694,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 55901 hom., cov: 32)

Exomes 𝑓: 0.93 ( 638258 hom. )

Consequence

PPCDC
NM_001301104.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.74

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:

PPCDC (HGNC:):

PPCDC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1492006E-6).

BP6

Variant 15-75044388-A-G is Benign according to our data. Variant chr15-75044388-A-G is described in ClinVar as [Benign]. Clinvar id is 1273465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPCDC	NM_021823.5 linkuse as main transcript	c.234A>G	p.Ile78Met	missense_variant, splice_region_variant	4/6	ENST00000342932.8	NP_068595.3	Q96CD2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPCDC	ENST00000342932.8 linkuse as main transcript	c.234A>G	p.Ile78Met	missense_variant, splice_region_variant	4/6	1	NM_021823.5	ENSP00000343190.3		Q96CD2-1

Frequencies

GnomAD3 genomes

AF:

0.845

AC:

128524

AN:

152034

Hom.:

55875

Cov.:

show subpopulations

Gnomad AFR

AF:

0.626

Gnomad AMI

AF:

0.964

Gnomad AMR

AF:

0.852

Gnomad ASJ

AF:

0.932

Gnomad EAS

AF:

0.876

Gnomad SAS

AF:

0.923

Gnomad FIN

AF:

0.935

Gnomad MID

AF:

0.930

Gnomad NFE

AF:

0.948

Gnomad OTH

AF:

0.872

GnomAD3 exomes

AF:

0.896

AC:

225062

AN:

251164

Hom.:

101946

AF XY:

0.906

AC XY:

123069

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.612

Gnomad AMR exome

AF:

0.801

Gnomad ASJ exome

AF:

0.925

Gnomad EAS exome

AF:

0.879

Gnomad SAS exome

AF:

0.922

Gnomad FIN exome

AF:

0.941

Gnomad NFE exome

AF:

0.949

Gnomad OTH exome

AF:

0.922

GnomAD4 exome

AF:

0.933

AC:

1362986

AN:

1461452

Hom.:

638258

Cov.:

AF XY:

0.933

AC XY:

678606

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.614

Gnomad4 AMR exome

AF:

0.808

Gnomad4 ASJ exome

AF:

0.926

Gnomad4 EAS exome

AF:

0.866

Gnomad4 SAS exome

AF:

0.924

Gnomad4 FIN exome

AF:

0.939

Gnomad4 NFE exome

AF:

0.951

Gnomad4 OTH exome

AF:

0.919

GnomAD4 genome

AF:

0.845

AC:

128603

AN:

152152

Hom.:

55901

Cov.:

AF XY:

0.848

AC XY:

63066

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.626

Gnomad4 AMR

AF:

0.852

Gnomad4 ASJ

AF:

0.932

Gnomad4 EAS

AF:

0.876

Gnomad4 SAS

AF:

0.924

Gnomad4 FIN

AF:

0.935

Gnomad4 NFE

AF:

0.948

Gnomad4 OTH

AF:

0.870

Alfa

AF:

0.913

Hom.:

76605

Bravo

AF:

0.827

TwinsUK

AF:

0.953

AC:

3534

ALSPAC

AF:

0.951

AC:

3667

ESP6500AA

AF:

0.630

AC:

2769

ESP6500EA

AF:

0.947

AC:

8133

ExAC

AF:

0.896

AC:

108825

Asia WGS

AF:

0.860

AC:

2990

AN:

3478

EpiCase

AF:

0.945

EpiControl

AF:

0.943

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 26, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.19

T;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.13

T;T

MetaRNN

Benign

0.0000011

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.22

N;.

PrimateAI

Benign

0.36

PROVEAN

Benign

0.87

N;N

REVEL

Benign

0.093

Sift

Benign

0.25

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.0

B;.

Vest4

0.082

MPC

0.11

ClinPred

0.0050

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.57

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over