10-15103856-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_183005.5(RPP38):ā€‹c.542C>Gā€‹(p.Ala181Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,613,792 control chromosomes in the GnomAD database, including 62,199 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.38 ( 15381 hom., cov: 32)
Exomes š‘“: 0.23 ( 46818 hom. )

Consequence

RPP38
NM_183005.5 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.78
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]

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=2.830223E-6).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RPP38NM_183005.5 linkuse as main transcriptc.542C>G p.Ala181Gly missense_variant 3/3 ENST00000378197.5 NP_892117.1 P78345

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RPP38ENST00000378197.5 linkuse as main transcriptc.542C>G p.Ala181Gly missense_variant 3/31 NM_183005.5 ENSP00000367439.4 P78345

Frequencies

GnomAD3 genomes
AF:
0.376
AC:
57186
AN:
151908
Hom.:
15320
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.767
Gnomad AMI
AF:
0.380
Gnomad AMR
AF:
0.248
Gnomad ASJ
AF:
0.326
Gnomad EAS
AF:
0.127
Gnomad SAS
AF:
0.171
Gnomad FIN
AF:
0.213
Gnomad MID
AF:
0.361
Gnomad NFE
AF:
0.230
Gnomad OTH
AF:
0.349
GnomAD3 exomes
AF:
0.249
AC:
62528
AN:
251326
Hom.:
10576
AF XY:
0.240
AC XY:
32649
AN XY:
135846
show subpopulations
Gnomad AFR exome
AF:
0.773
Gnomad AMR exome
AF:
0.164
Gnomad ASJ exome
AF:
0.306
Gnomad EAS exome
AF:
0.134
Gnomad SAS exome
AF:
0.191
Gnomad FIN exome
AF:
0.217
Gnomad NFE exome
AF:
0.235
Gnomad OTH exome
AF:
0.255
GnomAD4 exome
AF:
0.235
AC:
343146
AN:
1461766
Hom.:
46818
Cov.:
36
AF XY:
0.233
AC XY:
169413
AN XY:
727176
show subpopulations
Gnomad4 AFR exome
AF:
0.793
Gnomad4 AMR exome
AF:
0.173
Gnomad4 ASJ exome
AF:
0.309
Gnomad4 EAS exome
AF:
0.119
Gnomad4 SAS exome
AF:
0.195
Gnomad4 FIN exome
AF:
0.216
Gnomad4 NFE exome
AF:
0.225
Gnomad4 OTH exome
AF:
0.262
GnomAD4 genome
AF:
0.377
AC:
57303
AN:
152026
Hom.:
15381
Cov.:
32
AF XY:
0.369
AC XY:
27411
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.767
Gnomad4 AMR
AF:
0.247
Gnomad4 ASJ
AF:
0.326
Gnomad4 EAS
AF:
0.127
Gnomad4 SAS
AF:
0.171
Gnomad4 FIN
AF:
0.213
Gnomad4 NFE
AF:
0.230
Gnomad4 OTH
AF:
0.347
Alfa
AF:
0.226
Hom.:
2743
Bravo
AF:
0.396
TwinsUK
AF:
0.219
AC:
811
ALSPAC
AF:
0.242
AC:
932
ESP6500AA
AF:
0.755
AC:
3327
ESP6500EA
AF:
0.236
AC:
2031
ExAC
AF:
0.259
AC:
31423
Asia WGS
AF:
0.175
AC:
609
AN:
3478
EpiCase
AF:
0.238
EpiControl
AF:
0.243

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.015
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
16
DANN
Benign
0.55
DEOGEN2
Benign
0.026
T;T;T;T
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.44
FATHMM_MKL
Benign
0.24
N
LIST_S2
Benign
0.42
.;T;.;.
MetaRNN
Benign
0.0000028
T;T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
-2.9
N;N;N;N
MutationTaster
Benign
0.98
P;P;P;P
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
3.6
N;.;N;N
REVEL
Benign
0.22
Sift
Benign
1.0
T;.;T;T
Sift4G
Benign
1.0
T;T;T;T
Polyphen
0.0
B;B;B;B
Vest4
0.052
MPC
0.084
ClinPred
0.019
T
GERP RS
5.7
Varity_R
0.36
gMVP
0.63

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.

Other links and lift over

dbSNP: rs15772; hg19: chr10-15145855; COSMIC: COSV65381610; COSMIC: COSV65381610; API