1-42456582-C-T

Variant names:

• chr1-42456582-C-T
• rs767261512
• NM_024664.4:c.17C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001077447.3(PPCS):​c.-58C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000348 in 1,492,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: PPCS NM_001077447.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 1.77
• Publications: 0 publications found

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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04044801).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077447.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPCS	NM_024664.4	MANE Select	c.17C>T	p.Pro6Leu	missense	Exon 1 of 3	NP_078940.2	Q9HAB8-1
	PPCS	NM_001077447.3		c.-58C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001070915.1	Q9HAB8-2
	PPCS	NM_001287508.2		c.-154C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001274437.1	Q9HAB8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPCS	ENST00000372561.4	TSL:1 MANE Select	c.17C>T	p.Pro6Leu	missense	Exon 1 of 3	ENSP00000361642.3	Q9HAB8-1
	PPCS	ENST00000372560.3	TSL:1	c.17C>T	p.Pro6Leu	missense	Exon 1 of 2	ENSP00000361641.3	Q5VVM3
	PPCS	ENST00000472013.1	TSL:1	n.39C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152244 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000160 AC: 2 AN: 124766 AF XY: 0.0000296

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: 0.0000347

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000373 AC: 50 AN: 1339982 Hom.: 0 Cov.: 31 AF XY: 0.0000489 AC XY: 32 AN XY: 654606

African (AFR) AF: 0.00 AC: 0 AN: 29292

American (AMR) AF: 0.00 AC: 0 AN: 24026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19332

East Asian (EAS) AF: 0.00 AC: 0 AN: 36712

South Asian (SAS) AF: 0.00 AC: 0 AN: 68844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5248

European-Non Finnish (NFE) AF: 0.0000446 AC: 47 AN: 1054846

Other (OTH) AF: 0.0000545 AC: 3 AN: 55050

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152244 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74384

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000172 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.9	N
PhyloP100		1.8
PrimateAI	Benign	0.45	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.064
Sift	Benign	0.79	T
Sift4G	Benign	0.65	T
Polyphen		0.0	B
Vest4		0.10
MVP		0.29
MPC		0.65
ClinPred		0.056	T
GERP RS		4.1
PromoterAI		-0.19	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.043
gMVP		0.33
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs767261512; hg19: chr1-42922253;