Genetic Variant PPCS:p.Pro13Thr (chr1-42456602-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_024664.4(PPCS):c.37C>A(p.Pro13Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000441 in 1,361,692 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

PPCS
NM_024664.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.56

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.37C>A	p.Pro13Thr	missense	Exon 1 of 3	NP_078940.2	Q9HAB8-1
PPCS	NM_001287511.2		c.37C>A	p.Pro13Thr	missense	Exon 1 of 3	NP_001274440.1
PPCS	NM_001077447.3		c.-38C>A		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.37C>A	p.Pro13Thr	missense	Exon 1 of 3	ENSP00000361642.3	Q9HAB8-1
PPCS	ENST00000372560.3	TSL:1	c.37C>A	p.Pro13Thr	missense	Exon 1 of 2	ENSP00000361641.3	Q5VVM3
PPCS	ENST00000472013.1	TSL:1	n.59C>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000652

AC:

AN:

153468

AF XY:

0.0000119

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:

0.0000139

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000441

AC:

AN:

1361692

Hom.:

Cov.:

AF XY:

0.00000300

AC XY:

AN XY:

667778

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29820

American (AMR)

AF:

0.00

AC:

AN:

27566

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20114

East Asian (EAS)

AF:

0.00

AC:

AN:

37814

South Asian (SAS)

AF:

0.00

AC:

AN:

71480

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48202

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5300

European-Non Finnish (NFE)

AF:

0.00000563

AC:

AN:

1065628

Other (OTH)

AF:

0.00

AC:

AN:

55768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.79

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.1

PhyloP100

4.6

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.21

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.49

MutPred

0.46

Gain of phosphorylation at P13 (P = 0.0306)

MVP

0.29

MPC

1.8

ClinPred

0.99

GERP RS

5.3

PromoterAI

-0.032

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.77

gMVP

0.74

Mutation Taster

=70/30

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