rs1430236101

Variant names:

• chr1-42456595-C-T
• rs1430236101
• NM_024664.4:c.30C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-42456595-C-T
• chr1-42456595-C-G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_024664.4(PPCS):​c.30C>T​(p.Phe10Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000369 in 1,355,074 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: PPCS NM_024664.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.624
• Publications: 1 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 1-42456595-C-T is Benign according to our data. Variant chr1-42456595-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3011680.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.624 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPCS	NM_024664.4	MANE Select	c.30C>T	p.Phe10Phe	synonymous	Exon 1 of 3	NP_078940.2	Q9HAB8-1
	PPCS	NM_001287511.2		c.30C>T	p.Phe10Phe	synonymous	Exon 1 of 3	NP_001274440.1
	PPCS	NM_001077447.3		c.-45C>T		5_prime_UTR	Exon 1 of 3	NP_001070915.1	Q9HAB8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPCS	ENST00000372561.4	TSL:1 MANE Select	c.30C>T	p.Phe10Phe	synonymous	Exon 1 of 3	ENSP00000361642.3	Q9HAB8-1
	PPCS	ENST00000372560.3	TSL:1	c.30C>T	p.Phe10Phe	synonymous	Exon 1 of 2	ENSP00000361641.3	Q5VVM3
	PPCS	ENST00000472013.1	TSL:1	n.52C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000691 AC: 1 AN: 144770 AF XY: 0.00

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: 0.0000148

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000369 AC: 5 AN: 1355074 Hom.: 0 Cov.: 31 AF XY: 0.00000151 AC XY: 1 AN XY: 663822

African (AFR) AF: 0.00 AC: 0 AN: 29676

American (AMR) AF: 0.00 AC: 0 AN: 26578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19768

East Asian (EAS) AF: 0.00 AC: 0 AN: 37528

South Asian (SAS) AF: 0.00 AC: 0 AN: 70502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5286

European-Non Finnish (NFE) AF: 0.00000376 AC: 4 AN: 1062482

Other (OTH) AF: 0.0000180 AC: 1 AN: 55532

GnomAD4 genome Cov.: 33

Alfa AF: 0.000131 Hom.: 1

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.7
DANN	Benign	0.93
PhyloP100		-0.62
PromoterAI		-0.0068	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	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: rs1430236101; hg19: chr1-42922266; COSMIC: COSV65333450; COSMIC: COSV65333450;