Variant 10-97366141-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015179.4(RRP12):c.3484G>A(p.Gly1162Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 1,606,478 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

RRP12
NM_015179.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.963

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031057239).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RRP12	NM_015179.4 linkuse as main transcript	c.3484G>A	p.Gly1162Ser	missense_variant	29/34	ENST00000370992.9	NP_055994.2
RRP12	NM_001145114.1 linkuse as main transcript	c.3301G>A	p.Gly1101Ser	missense_variant	27/32		NP_001138586.1
RRP12	NM_001284337.2 linkuse as main transcript	c.3184G>A	p.Gly1062Ser	missense_variant	26/31		NP_001271266.1
RRP12	XM_047424903.1 linkuse as main transcript	c.3400G>A	p.Gly1134Ser	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.3484G>A	p.Gly1162Ser	missense_variant	29/34	1	NM_015179.4	ENSP00000360031	P1	Q5JTH9-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151596

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.0000162

AC:

AN:

246448

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133614

show subpopulations

Gnomad AFR exome

AF:

0.0000616

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:

0.0000186

AC:

AN:

1454882

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

724016

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000207

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151596

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74012

show subpopulations

Gnomad4 AFR

AF:

0.0000243

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:

0.0000843

Hom.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2023

The c.3484G>A (p.G1162S) alteration is located in exon 29 (coding exon 29) of the RRP12 gene. This alteration results from a G to A substitution at nucleotide position 3484, causing the glycine (G) at amino acid position 1162 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.6

DANN

Benign

0.57

DEOGEN2

Benign

0.010

T;.;T;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.66

.;T;T;T;T

M_CAP

Benign

0.0082

MetaRNN

Benign

0.031

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.0

L;.;L;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

0.69

.;N;N;N;.

REVEL

Benign

0.022

Sift

Benign

0.58

.;T;T;T;.

Sift4G

Benign

0.20

T;T;T;T;T

Polyphen

0.0030

B;B;B;.;.

Vest4

0.056

MutPred

0.20

Gain of phosphorylation at G1162 (P = 0.0112);.;Gain of phosphorylation at G1162 (P = 0.0112);.;.;

MVP

0.16

MPC

0.16

ClinPred

0.011

GERP RS

-2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.070

gMVP

0.064

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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