Variant 10-97366177-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.3448G>A(p.Ala1150Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000271 in 1,610,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

RRP12
NM_015179.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75

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:

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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=0.053187847).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRP12	NM_015179.4 linkuse as main transcript	c.3448G>A	p.Ala1150Thr	missense_variant	29/34	ENST00000370992.9	NP_055994.2	Q5JTH9-1B3KMR5
RRP12	NM_001145114.1 linkuse as main transcript	c.3265G>A	p.Ala1089Thr	missense_variant	27/32		NP_001138586.1	Q5JTH9-3B3KMR5
RRP12	NM_001284337.2 linkuse as main transcript	c.3148G>A	p.Ala1050Thr	missense_variant	26/31		NP_001271266.1	Q5JTH9-2B3KMR5
RRP12	XM_047424903.1 linkuse as main transcript	c.3364G>A	p.Ala1122Thr	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.3448G>A	p.Ala1150Thr	missense_variant	29/34	1	NM_015179.4	ENSP00000360031.4		Q5JTH9-1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

151800

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000324

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000153

AC:

AN:

249162

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

134900

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000516

Gnomad NFE exome

AF:

0.000281

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000282

AC:

412

AN:

1458582

Hom.:

Cov.:

AF XY:

0.000293

AC XY:

213

AN XY:

725756

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000797

Gnomad4 NFE exome

AF:

0.000350

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000158

AC:

AN:

151800

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74118

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000324

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000273

Hom.:

Bravo

AF:

0.000125

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

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

Jul 27, 2024

The c.3448G>A (p.A1150T) 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 3448, causing the alanine (A) at amino acid position 1150 to be replaced by a threonine (T). 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

0.077

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

T;.;T;.;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.88

.;D;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.053

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.;L;.;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.21

.;N;N;N;.

REVEL

Benign

0.066

Sift

Benign

0.25

.;T;T;T;.

Sift4G

Benign

0.39

T;T;T;T;D

Polyphen

0.089

B;B;B;.;.

Vest4

0.087

MVP

0.51

MPC

0.16

ClinPred

0.028

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.038

gMVP

0.078

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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