10-90893362-C-T

Variant summary

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

The NM_006413.5(RPP30):c.433-1413C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,968 control chromosomes in the GnomAD database, including 12,061 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 0.37 (12061 hom., cov: 31)
• Consequence: RPP30 NM_006413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPP30	NM_006413.5	c.433-1413C>T		intron_variant		ENST00000371703.8
RPP30	NM_001104546.2	c.433-1413C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPP30	ENST00000371703.8	c.433-1413C>T		intron_variant		1	NM_006413.5	P1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56183 AN: 151850 Hom.: 12063 Cov.: 31

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.370 AC: 56187 AN: 151968 Hom.: 12061 Cov.: 31 AF XY: 0.372 AC XY: 27591 AN XY: 74242

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.393

Alfa AF: 0.299 Hom.: 863

Bravo AF: 0.360

Asia WGS AF: 0.368 AC: 1282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.8
Dann	Benign	0.67

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: rs10509613; hg19: chr10-92653119;