rs4933620

Variant names:

• chr10-90900108-T-C
• rs4933620
• NM_006413.5:c.698-462T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006413.5(RPP30):​c.698-462T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,154 control chromosomes in the GnomAD database, including 4,122 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (4122 hom., cov: 33)
• Consequence: RPP30 NM_006413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

Genes affected

RPP30 (HGNC:17688): (ribonuclease P/MRP subunit p30) Enables ribonuclease P RNA binding activity. Contributes to ribonuclease P activity. Involved in tRNA 5'-leader removal. Part of multimeric ribonuclease P complex and ribonuclease MRP complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPP30	NM_006413.5	c.698-462T>C		intron_variant	Intron 10 of 10	ENST00000371703.8	NP_006404.1
RPP30	NM_001104546.2	c.698-462T>C		intron_variant	Intron 10 of 13		NP_001098016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPP30	ENST00000371703.8	c.698-462T>C		intron_variant	Intron 10 of 10	1	NM_006413.5	ENSP00000360768.3

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31571 AN: 152036 Hom.: 4114 Cov.: 33

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.230

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.208 AC: 31603 AN: 152154 Hom.: 4122 Cov.: 33 AF XY: 0.209 AC XY: 15553 AN XY: 74384

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.228

Alfa AF: 0.177 Hom.: 520

Bravo AF: 0.225

Asia WGS AF: 0.235 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.49

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

LitVar

Other links and lift over

dbSNP: rs4933620; hg19: chr10-92659865;