rs6986

chr6-30345563-G-C

Variant summary

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

The NM_024839.4(RPP21):c.231G>C(p.Gln77His) variant causes a missense change. The variant allele was found at a frequency of 0.24 in 1,538,976 control chromosomes in the GnomAD database, including 46,027 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.26 (5382 hom., cov: 27)
  • Exomes 𝑓: 0.24 (40645 hom.)
• Consequence: RPP21 NM_024839.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08

Genes affected

RPP21 (HGNC:21300): (ribonuclease P/MRP subunit p21) RPP21 is a protein subunit of nuclear ribonuclease P, which processes the 5-prime leader sequence of precursor tRNAs (Jarrous et al., 2001 [PubMed 11497433]).[supplied by OMIM, Jan 2009]

TRIM39-RPP21 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025838912).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPP21	NM_024839.4	c.231G>C	p.Gln77His	missense_variant	3/5	ENST00000442966.7
TRIM39-RPP21	NM_001199119.1	c.1278G>C	p.Gln426His	missense_variant	8/10
RPP21	NM_001199120.3	c.255G>C	p.Gln85His	missense_variant	3/5
RPP21	NM_001199121.3	c.231G>C	p.Gln77His	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPP21	ENST00000442966.7	c.231G>C	p.Gln77His	missense_variant	3/5	1	NM_024839.4	P1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39523 AN: 150426 Hom.: 5382 Cov.: 27

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.302

GnomAD3 exomes AF: 0.239 AC: 42860 AN: 179358 Hom.: 5681 AF XY: 0.249 AC XY: 24133 AN XY: 96996

Gnomad AFR exome AF: 0.322

Gnomad AMR exome AF: 0.156

Gnomad ASJ exome AF: 0.355

Gnomad EAS exome AF: 0.179

Gnomad SAS exome AF: 0.366

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.231

Gnomad OTH exome AF: 0.254

GnomAD4 exome AF: 0.237 AC: 329143 AN: 1388430 Hom.: 40645 Cov.: 51 AF XY: 0.242 AC XY: 166622 AN XY: 687246

Gnomad4 AFR exome AF: 0.345

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.370

Gnomad4 EAS exome AF: 0.126

Gnomad4 SAS exome AF: 0.371

Gnomad4 FIN exome AF: 0.191

Gnomad4 NFE exome AF: 0.226

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.263 AC: 39522 AN: 150546 Hom.: 5382 Cov.: 27 AF XY: 0.261 AC XY: 19164 AN XY: 73504

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.299

Alfa AF: 0.247 Hom.: 3614

Bravo AF: 0.268

TwinsUK AF: 0.219 AC: 812

ALSPAC AF: 0.208 AC: 800

ESP6500AA AF: 0.317 AC: 952

ESP6500EA AF: 0.222 AC: 1197

ExAC AF: 0.197 AC: 22176

Asia WGS AF: 0.273 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	23
Dann	Uncertain	0.99
Eigen	Benign	0.081
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.93	D
MetaRNN	Benign	0.0026	T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	0.34	P;P;P;P
Sift4G	Benign	0.061	T;T;T;T;T
Polyphen		0.24, 0.0040, 0.11	.;.;B;B;B
Vest4		0.14
MutPred		0.15		.;.;Gain of sheet (P = 0.0049);.;Gain of sheet (P = 0.0049);
MPC		0.50
ClinPred		0.032	T
GERP RS		4.7
Varity_R		0.44
gMVP		0.45

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

LitVar

Other links and lift over

dbSNP: rs6986; hg19: chr6-30313340; COSMIC: COSV64954877; COSMIC: COSV64954877;