rs4933617

Positions:

• chr10-90886965-G-T

Variant summary

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

The NM_006413.5(RPP30):​c.432+1064G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 150,244 control chromosomes in the GnomAD database, including 29,124 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 0.60 (29124 hom., cov: 27)
• Consequence: RPP30 NM_006413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-1.07).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPP30	NM_006413.5	c.432+1064G>T		intron_variant		ENST00000371703.8
RPP30	NM_001104546.2	c.432+1064G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPP30	ENST00000371703.8	c.432+1064G>T		intron_variant		1	NM_006413.5	P1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 90102 AN: 150126 Hom.: 29080 Cov.: 27

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.600 AC: 90200 AN: 150244 Hom.: 29124 Cov.: 27 AF XY: 0.596 AC XY: 43758 AN XY: 73390

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.575

Alfa AF: 0.566 Hom.: 3246

Bravo AF: 0.619

Asia WGS AF: 0.515 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.39
DANN	Benign	0.20

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: rs4933617; hg19: chr10-92646722; COSMIC: COSV53295126;