1-42456601-G-A

Variant names:

• chr1-42456601-G-A
• rs72950587
• NM_024664.4:c.36G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_024664.4(PPCS):​c.36G>A​(p.Gln12Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00267 in 1,513,260 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (52 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (42 hom.)
• Consequence: PPCS NM_024664.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.141

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]

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-42456601-G-A is Benign according to our data. Variant chr1-42456601-G-A is described in ClinVar as [Benign]. Clinvar id is 1537987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.141 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPCS	NM_024664.4	c.36G>A	p.Gln12Gln	synonymous_variant	Exon 1 of 3	ENST00000372561.4	NP_078940.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPCS	ENST00000372561.4	c.36G>A	p.Gln12Gln	synonymous_variant	Exon 1 of 3	1	NM_024664.4	ENSP00000361642.3

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2187 AN: 152236 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00451

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00956

GnomAD2 exomes AF: 0.00428 AC: 652 AN: 152250 AF XY: 0.00336

Gnomad AFR exome AF: 0.0510

Gnomad AMR exome AF: 0.00159

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000561

Gnomad OTH exome AF: 0.00174

GnomAD4 exome AF: 0.00135 AC: 1838 AN: 1360906 Hom.: 42 Cov.: 31 AF XY: 0.00116 AC XY: 771 AN XY: 667342

Gnomad4 AFR exome AF: 0.0539 AC: 1605 AN: 29778

Gnomad4 AMR exome AF: 0.00200 AC: 55 AN: 27462

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 20068

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 37812

Gnomad4 SAS exome AF: 0.0000840 AC: 6 AN: 71398

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 48116

Gnomad4 NFE exome AF: 0.0000244 AC: 26 AN: 1065252

Gnomad4 Remaining exome AF: 0.00248 AC: 138 AN: 55720

GnomAD4 genome AF: 0.0144 AC: 2195 AN: 152354 Hom.: 52 Cov.: 32 AF XY: 0.0139 AC XY: 1033 AN XY: 74504

Gnomad4 AFR AF: 0.0506 AC: 0.0505772 AN: 0.0505772

Gnomad4 AMR AF: 0.00451 AC: 0.00450686 AN: 0.00450686

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000294 AC: 0.0000293979 AN: 0.0000293979

Gnomad4 OTH AF: 0.00946 AC: 0.00946074 AN: 0.00946074

Alfa AF: 0.00594 Hom.: 7

Bravo AF: 0.0166

Asia WGS AF: 0.00520 AC: 19 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PPCS-related disorder Benign:1

Feb 22, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.1
DANN	Benign	0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs72950587; hg19: chr1-42922272;