Genetic Variant PPCS:p.Pro14Leu (chr1-42456606-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024664.4(PPCS):c.41C>T(p.Pro14Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,371,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

PPCS
NM_024664.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.138

Publications

1 publications found

Variant links:

Genes affected

PPCS (HGNC:25686): (phosphopantothenoylcysteine synthetase) Biosynthesis of coenzyme A (CoA) from pantothenic acid (vitamin B5) is an essential universal pathway in prokaryotes and eukaryotes. PPCS (EC 6.3.2.5), one of the last enzymes in this pathway, converts phosphopantothenate to phosphopantothenoylcysteine (Daugherty et al., 2002 [PubMed 11923312]).[supplied by OMIM, Mar 2008]

PPCS links:

CCDC30 (HGNC:26103): (coiled-coil domain containing 30)

CCDC30 links:

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ACMG classification

Classification was made for transcript

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=0.10939956).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024664.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPCS	NM_024664.4	MANE Select	c.41C>T	p.Pro14Leu	missense	Exon 1 of 3	NP_078940.2	Q9HAB8-1
PPCS	NM_001287511.2		c.41C>T	p.Pro14Leu	missense	Exon 1 of 3	NP_001274440.1
PPCS	NM_001077447.3		c.-34C>T		5_prime_UTR	Exon 1 of 3	NP_001070915.1	Q9HAB8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPCS	ENST00000372561.4	TSL:1 MANE Select	c.41C>T	p.Pro14Leu	missense	Exon 1 of 3	ENSP00000361642.3	Q9HAB8-1
PPCS	ENST00000372560.3	TSL:1	c.41C>T	p.Pro14Leu	missense	Exon 1 of 2	ENSP00000361641.3	Q5VVM3
PPCS	ENST00000472013.1	TSL:1	n.63C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000622

AC:

AN:

160880

AF XY:

0.0000113

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000146

AC:

AN:

1371202

Hom.:

Cov.:

AF XY:

0.00000297

AC XY:

AN XY:

673922

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30130

American (AMR)

AF:

0.00

AC:

AN:

28936

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20514

East Asian (EAS)

AF:

0.00

AC:

AN:

38264

South Asian (SAS)

AF:

0.0000137

AC:

AN:

72762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5348

European-Non Finnish (NFE)

AF:

9.34e-7

AC:

AN:

1070540

Other (OTH)

AF:

0.00

AC:

AN:

56148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000840

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.77

M_CAP

Benign

0.037

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

PhyloP100

0.14

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.12

Sift

Uncertain

0.012

Sift4G

Uncertain

0.042

Polyphen

0.0050

Vest4

0.27

MutPred

0.37

Loss of disorder (P = 0.005)

MVP

0.29

MPC

0.66

ClinPred

0.14

GERP RS

4.4

PromoterAI

0.049

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.14

gMVP

0.37

Mutation Taster

=89/11

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over