rs6986

Variant names:

• chr6-30345563-G-C
• rs6986
• NM_024839.4:c.231G>C

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 38 publications found

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:38845): (TRIM39-RPP21 readthrough) This locus represents naturally occurring read-through transcription between the neighboring TRIM39 (tripartite motif-containing 39) and RPP21 (ribonuclease P/MRP 21kDa subunit) genes on chromosome 6. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024839.4. 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
	RPP21	NM_024839.4	MANE Select	c.231G>C	p.Gln77His	missense	Exon 3 of 5	NP_079115.1
	TRIM39-RPP21	NM_001199119.1		c.1278G>C	p.Gln426His	missense	Exon 8 of 10	NP_001186048.1
	RPP21	NM_001199120.3		c.255G>C	p.Gln85His	missense	Exon 3 of 5	NP_001186049.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPP21	ENST00000442966.7	TSL:1 MANE Select	c.231G>C	p.Gln77His	missense	Exon 3 of 5	ENSP00000403833.2
	TRIM39-RPP21	ENST00000623385.3	TSL:5	c.1278G>C	p.Gln426His	missense	Exon 9 of 11	ENSP00000485378.1
	RPP21	ENST00000436442.2	TSL:1	c.231G>C	p.Gln77His	missense	Exon 3 of 5	ENSP00000397778.2

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

GnomAD2 exomes AF: 0.239 AC: 42860 AN: 179358 AF XY: 0.249

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 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

African (AFR) AF: 0.345 AC: 10834 AN: 31392

American (AMR) AF: 0.167 AC: 6505 AN: 38938

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 9106 AN: 24610

East Asian (EAS) AF: 0.126 AC: 4170 AN: 33216

South Asian (SAS) AF: 0.371 AC: 30083 AN: 81156

European-Finnish (FIN) AF: 0.191 AC: 8573 AN: 44922

Middle Eastern (MID) AF: 0.413 AC: 2289 AN: 5538

European-Non Finnish (NFE) AF: 0.226 AC: 242699 AN: 1071980

Other (OTH) AF: 0.263 AC: 14884 AN: 56678

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

African (AFR) AF: 0.337 AC: 13811 AN: 41002

American (AMR) AF: 0.217 AC: 3297 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1191 AN: 3458

East Asian (EAS) AF: 0.175 AC: 878 AN: 5022

South Asian (SAS) AF: 0.361 AC: 1705 AN: 4718

European-Finnish (FIN) AF: 0.173 AC: 1777 AN: 10260

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16004 AN: 67608

Other (OTH) AF: 0.299 AC: 626 AN: 2092

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 v4.9

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
DEOGEN2	Benign	0.011	T
Eigen	Benign	0.081
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.93	D
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.1
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.040
Sift	Benign	0.46	T
Sift4G	Benign	0.061	T
Polyphen		0.24	B
Vest4		0.14
MutPred		0.15		Gain of sheet (P = 0.0049)
MPC		0.50
ClinPred		0.032	T
GERP RS		4.7
PromoterAI		0.034	Neutral
Varity_R		0.44
gMVP		0.45
Mutation Taster		=97/3	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: rs6986; hg19: chr6-30313340; COSMIC: COSV64954877; COSMIC: COSV64954877;