1-42473350-C-G

Variant names:

• chr1-42473350-C-G
• rs3748846
• NM_001395517.1:c.-91-7111C>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001287511.2(PPCS):​c.*106C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,036,594 control chromosomes in the GnomAD database, including 12,892 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1478 hom., cov: 32)
  • Exomes 𝑓: 0.16 (11414 hom.)
• Consequence: PPCS NM_001287511.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.489

Genes affected

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

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-42473350-C-G is Benign according to our data. Variant chr1-42473350-C-G is described in ClinVar as [Benign]. Clinvar id is 1263588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC30	NM_001395517.1	c.-91-7111C>G		intron_variant	Intron 1 of 20	ENST00000657597.2	NP_001382446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC30	ENST00000657597.2	c.-91-7111C>G		intron_variant	Intron 1 of 20		NM_001395517.1	ENSP00000499662.2

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19803 AN: 152076 Hom.: 1481 Cov.: 32

Gnomad AFR AF: 0.0695

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.153

GnomAD4 exome AF: 0.163 AC: 144077 AN: 884400 Hom.: 11414 Cov.: 12 AF XY: 0.162 AC XY: 68484 AN XY: 422502

Gnomad4 AFR exome AF: 0.0712

Gnomad4 AMR exome AF: 0.157

Gnomad4 ASJ exome AF: 0.199

Gnomad4 EAS exome AF: 0.168

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.130 AC: 19800 AN: 152194 Hom.: 1478 Cov.: 32 AF XY: 0.128 AC XY: 9486 AN XY: 74390

Gnomad4 AFR AF: 0.0695

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.152

Alfa AF: 0.142 Hom.: 213

Bravo AF: 0.136

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.5
DANN	Benign	0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3748846; hg19: chr1-42939021;