Variant rs10242 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_183005.5(RPP38):c.635T>C(p.Ile212Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0268 in 1,614,070 control chromosomes in the GnomAD database, including 631 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.024 ( 65 hom., cov: 32)

Exomes 𝑓: 0.027 ( 566 hom. )

Consequence

RPP38
NM_183005.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00100

Variant links:

Genes affected

RPP38 (HGNC:30329): (ribonuclease P/MRP subunit p38) Enables ribonuclease P RNA binding activity. Contributes to ribonuclease P activity. Involved in tRNA 5'-leader removal. Located in fibrillar center. Part of multimeric ribonuclease P complex. [provided by Alliance of Genome Resources, Apr 2022]

RPP38 links:

NMT2 (HGNC:7858): (N-myristoyltransferase 2) This gene encodes one of two N-myristoyltransferase proteins. N-terminal myristoylation is a lipid modification that is involved in regulating the function and localization of signaling proteins. The encoded protein catalyzes the addition of a myristoyl group to the N-terminal glycine residue of many signaling proteins, including the human immunodeficiency virus type 1 (HIV-1) proteins, Gag and Nef. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

NMT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020759702).

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0235 (3579/152258) while in subpopulation AMR AF= 0.0333 (509/15288). AF 95% confidence interval is 0.0309. There are 65 homozygotes in gnomad4. There are 1794 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3579 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPP38	NM_183005.5 link	c.635T>C	p.Ile212Thr	missense_variant	3/3	ENST00000378197.5	NP_892117.1	P78345

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPP38	ENST00000378197.5 link	c.635T>C	p.Ile212Thr	missense_variant	3/3	1	NM_183005.5	ENSP00000367439.4		P78345

Frequencies

GnomAD3 genomes

AF:

0.0235

AC:

3577

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00569

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0333

Gnomad ASJ

AF:

0.0329

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00766

Gnomad FIN

AF:

0.0485

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0306

Gnomad OTH

AF:

0.0306

GnomAD3 exomes

AF:

0.0252

AC:

6323

AN:

251388

Hom.:

AF XY:

0.0249

AC XY:

3384

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00418

Gnomad AMR exome

AF:

0.0217

Gnomad ASJ exome

AF:

0.0291

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00764

Gnomad FIN exome

AF:

0.0488

Gnomad NFE exome

AF:

0.0325

Gnomad OTH exome

AF:

0.0364

GnomAD4 exome

AF:

0.0271

AC:

39608

AN:

1461812

Hom.:

566

Cov.:

AF XY:

0.0267

AC XY:

19439

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00571

Gnomad4 AMR exome

AF:

0.0226

Gnomad4 ASJ exome

AF:

0.0291

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00868

Gnomad4 FIN exome

AF:

0.0463

Gnomad4 NFE exome

AF:

0.0293

Gnomad4 OTH exome

AF:

0.0259

GnomAD4 genome

AF:

0.0235

AC:

3579

AN:

152258

Hom.:

Cov.:

AF XY:

0.0241

AC XY:

1794

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00570

Gnomad4 AMR

AF:

0.0333

Gnomad4 ASJ

AF:

0.0329

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00767

Gnomad4 FIN

AF:

0.0485

Gnomad4 NFE

AF:

0.0306

Gnomad4 OTH

AF:

0.0302

Alfa

AF:

0.0292

Hom.:

194

Bravo

AF:

0.0210

TwinsUK

AF:

0.0343

AC:

127

ALSPAC

AF:

0.0327

AC:

126

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.0287

AC:

247

ExAC

AF:

0.0251

AC:

3046

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0357

EpiControl

AF:

0.0327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.010

DANN

Benign

0.49

DEOGEN2

Benign

0.0026

T;T;T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.29

.;T;.;.

MetaRNN

Benign

0.0021

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.065

N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

0.35

N;.;N;N

REVEL

Benign

0.11

Sift

Benign

0.85

T;.;T;T

Sift4G

Benign

0.72

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.023

MPC

0.11

ClinPred

0.0051

GERP RS

-5.2

Varity_R

0.041

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over