rs4144422

chr10-90885930-A-G

Variant summary

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

The NM_006413.5(RPP30):c.432+29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,388,106 control chromosomes in the GnomAD database, including 33,026 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 0.26 (5907 hom., cov: 32)
  • Exomes 𝑓: 0.20 (27119 hom.)
• Consequence: RPP30 NM_006413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPP30	NM_006413.5	c.432+29A>G		intron_variant		ENST00000371703.8
RPP30	NM_001104546.2	c.432+29A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPP30	ENST00000371703.8	c.432+29A>G		intron_variant		1	NM_006413.5	P1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39553 AN: 152016 Hom.: 5890 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.225

GnomAD3 exomes AF: 0.213 AC: 45537 AN: 213832 Hom.: 5208 AF XY: 0.212 AC XY: 24764 AN XY: 116650

Gnomad AFR exome AF: 0.431

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.185

Gnomad EAS exome AF: 0.158

Gnomad SAS exome AF: 0.224

Gnomad FIN exome AF: 0.168

Gnomad NFE exome AF: 0.209

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.204 AC: 252522 AN: 1235972 Hom.: 27119 Cov.: 16 AF XY: 0.205 AC XY: 128297 AN XY: 624374

Gnomad4 AFR exome AF: 0.423

Gnomad4 AMR exome AF: 0.162

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.201

Gnomad4 OTH exome AF: 0.209

GnomAD4 genome AF: 0.260 AC: 39615 AN: 152134 Hom.: 5907 Cov.: 32 AF XY: 0.257 AC XY: 19101 AN XY: 74386

Gnomad4 AFR AF: 0.420

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.225

Alfa AF: 0.239 Hom.: 1009

Bravo AF: 0.266

Asia WGS AF: 0.197 AC: 685 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	13
Dann	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4144422; hg19: chr10-92645687; COSMIC: COSV53295134;