10-90873142-T-G

Variant names:

• chr10-90873142-T-G
• rs4586057
• NM_006413.5:c.82+1074T>G

Variant summary

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

The NM_006413.5(RPP30):​c.82+1074T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,100 control chromosomes in the GnomAD database, including 5,848 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 (5848 hom., cov: 32)
• Consequence: RPP30 NM_006413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006413.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPP30	NM_006413.5	MANE Select	c.82+1074T>G		intron	N/A	NP_006404.1
	RPP30	NM_001104546.2		c.82+1074T>G		intron	N/A	NP_001098016.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPP30	ENST00000371703.8	TSL:1 MANE Select	c.82+1074T>G		intron	N/A	ENSP00000360768.3
	RPP30	ENST00000413330.5	TSL:5	c.82+1074T>G		intron	N/A	ENSP00000389182.1
	RPP30	ENST00000277882.7	TSL:5	c.148+1008T>G		intron	N/A	ENSP00000277882.3

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39392 AN: 151982 Hom.: 5830 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.259 AC: 39455 AN: 152100 Hom.: 5848 Cov.: 32 AF XY: 0.255 AC XY: 18994 AN XY: 74344

African (AFR) AF: 0.417 AC: 17275 AN: 41448

American (AMR) AF: 0.203 AC: 3105 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 647 AN: 3470

East Asian (EAS) AF: 0.159 AC: 822 AN: 5176

South Asian (SAS) AF: 0.215 AC: 1039 AN: 4822

European-Finnish (FIN) AF: 0.166 AC: 1760 AN: 10590

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14172 AN: 67986

Other (OTH) AF: 0.225 AC: 477 AN: 2116

Alfa AF: 0.220 Hom.: 10801

Bravo AF: 0.266

Asia WGS AF: 0.198 AC: 689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.7
DANN	Benign	0.58
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4586057; hg19: chr10-92632899;