chr10-15103856-C-G

Position:

• chr10-15103856-C-G

Variant summary

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

The NM_183005.5(RPP38):​c.542C>G​(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: 𝑓 0.38 (15381 hom., cov: 32)
  • Exomes 𝑓: 0.23 (46818 hom.)
• Consequence: RPP38 NM_183005.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.78

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]

NMT2 (HGNC:):

ACMG classification

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
RPP38	NM_183005.5	c.542C>G	p.Ala181Gly	missense_variant	3/3	ENST00000378197.5	NP_892117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPP38	ENST00000378197.5	c.542C>G	p.Ala181Gly	missense_variant	3/3	1	NM_183005.5	ENSP00000367439.4

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57186 AN: 151908 Hom.: 15320 Cov.: 32

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

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

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

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

Other links and lift over

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