rs10509612

chr10-90885603-G-A

Variant summary

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

The NM_006413.5(RPP30):c.343-209G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,032 control chromosomes in the GnomAD database, including 4,358 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 (4358 hom., cov: 32)
• Consequence: RPP30 NM_006413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPP30	NM_006413.5	c.343-209G>A		intron_variant		ENST00000371703.8
RPP30	NM_001104546.2	c.343-209G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPP30	ENST00000371703.8	c.343-209G>A		intron_variant		1	NM_006413.5	P1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32219 AN: 151914 Hom.: 4349 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.0947

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.212 AC: 32252 AN: 152032 Hom.: 4358 Cov.: 32 AF XY: 0.214 AC XY: 15876 AN XY: 74310

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.231

Alfa AF: 0.169 Hom.: 365

Bravo AF: 0.230

Asia WGS AF: 0.236 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.4
Dann	Benign	0.43

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: rs10509612; hg19: chr10-92645360;