10-90871714-T-C

Variant names:

• chr10-90871714-T-C
• rs4933199
• ENST00000413330.5:c.-273T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000413330.5(RPP30):​c.-273T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 438,972 control chromosomes in the GnomAD database, including 8,528 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 (4092 hom., cov: 33)
  • Exomes 𝑓: 0.16 (4436 hom.)
• Consequence: RPP30 ENST00000413330.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPP30	ENST00000413330.5	c.-273T>C		upstream_gene_variant		5		ENSP00000389182.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31462 AN: 152102 Hom.: 4084 Cov.: 33

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.156 AC: 44627 AN: 286752 Hom.: 4436 Cov.: 0 AF XY: 0.156 AC XY: 22989 AN XY: 147578

African (AFR) AF: 0.354 AC: 3118 AN: 8808

American (AMR) AF: 0.246 AC: 2811 AN: 11428

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 1530 AN: 9336

East Asian (EAS) AF: 0.289 AC: 6040 AN: 20896

South Asian (SAS) AF: 0.213 AC: 4445 AN: 20828

European-Finnish (FIN) AF: 0.118 AC: 2394 AN: 20298

Middle Eastern (MID) AF: 0.207 AC: 283 AN: 1366

European-Non Finnish (NFE) AF: 0.120 AC: 21101 AN: 175888

Other (OTH) AF: 0.162 AC: 2905 AN: 17904

GnomAD4 genome AF: 0.207 AC: 31493 AN: 152220 Hom.: 4092 Cov.: 33 AF XY: 0.208 AC XY: 15505 AN XY: 74428

African (AFR) AF: 0.355 AC: 14749 AN: 41514

American (AMR) AF: 0.224 AC: 3431 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3472

East Asian (EAS) AF: 0.277 AC: 1433 AN: 5180

South Asian (SAS) AF: 0.232 AC: 1118 AN: 4824

European-Finnish (FIN) AF: 0.121 AC: 1285 AN: 10606

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8305 AN: 68006

Other (OTH) AF: 0.226 AC: 478 AN: 2114

Alfa AF: 0.112 Hom.: 274

Bravo AF: 0.224

Asia WGS AF: 0.236 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.9
DANN	Benign	0.67
PhyloP100		-0.31
PromoterAI		0.0086	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4933199; hg19: chr10-92631471;