Variant chr10-97366155-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000370992.9(RRP12):c.3470G>A(p.Arg1157Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,607,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

RRP12
ENST00000370992.9 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.248

Variant links:

Genes affected

RRP12 (HGNC:29100): (ribosomal RNA processing 12 homolog) Enables RNA binding activity. Predicted to be involved in rRNA processing. Located in cytosol; nucleolus; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RRP12 links:

RRP12 (HGNC:):

RRP12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03772822).

BP6

Variant 10-97366155-C-T is Benign according to our data. Variant chr10-97366155-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2470670.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRP12	NM_015179.4 linkuse as main transcript	c.3470G>A	p.Arg1157Lys	missense_variant	29/34	ENST00000370992.9	NP_055994.2	Q5JTH9-1B3KMR5
RRP12	NM_001145114.1 linkuse as main transcript	c.3287G>A	p.Arg1096Lys	missense_variant	27/32		NP_001138586.1	Q5JTH9-3B3KMR5
RRP12	NM_001284337.2 linkuse as main transcript	c.3170G>A	p.Arg1057Lys	missense_variant	26/31		NP_001271266.1	Q5JTH9-2B3KMR5
RRP12	XM_047424903.1 linkuse as main transcript	c.3386G>A	p.Arg1129Lys	missense_variant	28/33		XP_047280859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRP12	ENST00000370992.9 linkuse as main transcript	c.3470G>A	p.Arg1157Lys	missense_variant	29/34	1	NM_015179.4	ENSP00000360031.4		Q5JTH9-1

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151444

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247786

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134246

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000254

AC:

AN:

1456360

Hom.:

Cov.:

AF XY:

0.0000207

AC XY:

AN XY:

724698

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000306

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151444

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73942

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 13, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.014

T;.;T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.74

.;T;T;T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.038

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.71

N;.;N;.;.

MutationTaster

Benign

0.97

N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.11

.;N;N;N;.

REVEL

Benign

0.014

Sift

Benign

0.89

.;T;T;T;.

Sift4G

Benign

0.76

T;T;T;T;D

Polyphen

0.0040

B;B;B;.;.

Vest4

0.10

MutPred

0.38

Gain of ubiquitination at R1157 (P = 0.0018);.;Gain of ubiquitination at R1157 (P = 0.0018);.;.;

MVP

0.23

MPC

0.16

ClinPred

0.020

GERP RS

-1.9

Varity_R

0.050

gMVP

0.078

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over