dbSNP rs4144422: RPP30:c.432+29A>G (chr10-90885930-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006413.5(RPP30):c.432+29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,388,106 control chromosomes in the GnomAD database, including 33,026 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 ( 5907 hom., cov: 32)

Exomes 𝑓: 0.20 ( 27119 hom. )

Consequence

RPP30
NM_006413.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.114

Publications

7 publications found

Variant links:

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]

RPP30 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPP30	NM_006413.5 link	c.432+29A>G		intron_variant	Intron 6 of 10	ENST00000371703.8	NP_006404.1	P78346-1
RPP30	NM_001104546.2 link	c.432+29A>G		intron_variant	Intron 6 of 13		NP_001098016.1	P78346-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPP30	ENST00000371703.8 link	c.432+29A>G		intron_variant	Intron 6 of 10	1	NM_006413.5	ENSP00000360768.3		P78346-1

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

39553

AN:

152016

Hom.:

5890

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.159

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.167

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.225

GnomAD2 exomes

AF:

0.213

AC:

45537

AN:

213832

AF XY:

0.212

show subpopulations

Gnomad AFR exome

AF:

0.431

Gnomad AMR exome

AF:

0.165

Gnomad ASJ exome

AF:

0.185

Gnomad EAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.209

Gnomad OTH exome

AF:

0.208

GnomAD4 exome

AF:

0.204

AC:

252522

AN:

1235972

Hom.:

27119

Cov.:

AF XY:

0.205

AC XY:

128297

AN XY:

624374

show subpopulations

African (AFR)

AF:

0.423

AC:

11670

AN:

27586

American (AMR)

AF:

0.162

AC:

5413

AN:

33492

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

4241

AN:

23780

East Asian (EAS)

AF:

0.164

AC:

6167

AN:

37634

South Asian (SAS)

AF:

0.227

AC:

17234

AN:

75822

European-Finnish (FIN)

AF:

0.167

AC:

8502

AN:

50908

Middle Eastern (MID)

AF:

0.228

AC:

1194

AN:

5248

European-Non Finnish (NFE)

AF:

0.201

AC:

187081

AN:

928748

Other (OTH)

AF:

0.209

AC:

11020

AN:

52754

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

9729

19458

29187

38916

48645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6058

12116

18174

24232

30290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.260

AC:

39615

AN:

152134

Hom.:

5907

Cov.:

AF XY:

0.257

AC XY:

19101

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.420

AC:

17400

AN:

41476

American (AMR)

AF:

0.204

AC:

3120

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

647

AN:

3472

East Asian (EAS)

AF:

0.159

AC:

822

AN:

5178

South Asian (SAS)

AF:

0.216

AC:

1038

AN:

4810

European-Finnish (FIN)

AF:

0.167

AC:

1769

AN:

10588

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14185

AN:

67998

Other (OTH)

AF:

0.225

AC:

476

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1409

2819

4228

5638

7047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

390

780

1170

1560

1950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.243

Hom.:

1077

Bravo

AF:

0.266

Asia WGS

AF:

0.197

AC:

685

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over