chr10-90884615-G-A

Variant names:

• chr10-90884615-G-A
• rs12766523
• NM_006413.5:c.343-1197G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006413.5(RPP30):​c.343-1197G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,088 control chromosomes in the GnomAD database, including 4,125 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 (4125 hom., cov: 32)
• Consequence: RPP30 NM_006413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.51
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 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.343-1197G>A		intron	N/A	NP_006404.1
	RPP30	NM_001104546.2		c.343-1197G>A		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.343-1197G>A		intron	N/A	ENSP00000360768.3
	RPP30	ENST00000413330.5	TSL:5	c.343-1197G>A		intron	N/A	ENSP00000389182.1
	RPP30	ENST00000277882.7	TSL:5	c.409-1197G>A		intron	N/A	ENSP00000277882.3

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31561 AN: 151970 Hom.: 4117 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.208 AC: 31592 AN: 152088 Hom.: 4125 Cov.: 32 AF XY: 0.209 AC XY: 15543 AN XY: 74330

African (AFR) AF: 0.358 AC: 14845 AN: 41466

American (AMR) AF: 0.225 AC: 3432 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3470

East Asian (EAS) AF: 0.276 AC: 1424 AN: 5158

South Asian (SAS) AF: 0.232 AC: 1116 AN: 4816

European-Finnish (FIN) AF: 0.122 AC: 1287 AN: 10584

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

European-Non Finnish (NFE) AF: 0.122 AC: 8315 AN: 67998

Other (OTH) AF: 0.227 AC: 479 AN: 2114

Alfa AF: 0.196 Hom.: 562

Bravo AF: 0.225

Asia WGS AF: 0.236 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Benign	0.69
PhyloP100		3.5
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: rs12766523; hg19: chr10-92644372;