10-90908517-G-T

Position:

• chr10-90908517-G-T

Variant summary

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

The NM_001104546.2(RPP30):​c.*3230G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,890 control chromosomes in the GnomAD database, including 4,599 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 0.24 (4599 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: RPP30 NM_001104546.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPP30	NM_001104546.2	c.*3230G>T		3_prime_UTR_variant	14/14		NP_001098016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPP30	ENST00000470933.1	n.588G>T		non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36171 AN: 151772 Hom.: 4585 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.204

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.239 AC: 36228 AN: 151890 Hom.: 4599 Cov.: 32 AF XY: 0.236 AC XY: 17529 AN XY: 74234

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.204

Alfa AF: 0.231 Hom.: 497

Bravo AF: 0.241

Asia WGS AF: 0.189 AC: 659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.1
DANN	Benign	0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11186361; hg19: chr10-92668274;