Variant 14-73106278-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000261973.12(RBM25):c.1460G>C(p.Arg487Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,000 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RBM25
ENST00000261973.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.87

Variant links:

Genes affected

RBM25 (HGNC:23244): (RNA binding motif protein 25) Enables mRNA binding activity. Involved in regulation of alternative mRNA splicing, via spliceosome and regulation of apoptotic process. Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

RBM25 links:

RBM25 (HGNC:):

RBM25 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM25	NM_021239.3 linkuse as main transcript	c.1460G>C	p.Arg487Thr	missense_variant	12/19	ENST00000261973.12	NP_067062.1	P49756-1
RBM25	XM_011537044.4 linkuse as main transcript	c.1460G>C	p.Arg487Thr	missense_variant	13/20		XP_011535346.1	P49756-1
RBM25	XM_047431641.1 linkuse as main transcript	c.1460G>C	p.Arg487Thr	missense_variant	12/16		XP_047287597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM25	ENST00000261973.12 linkuse as main transcript	c.1460G>C	p.Arg487Thr	missense_variant	12/19	1	NM_021239.3	ENSP00000261973.7		P49756-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151882

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:

0.00000866

AC:

AN:

230876

Hom.:

AF XY:

0.00000792

AC XY:

AN XY:

126246

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:

0.0000186

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000163

AC:

AN:

1409142

Hom.:

Cov.:

AF XY:

0.0000185

AC XY:

AN XY:

701834

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000399

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.0000195

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152000

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74308

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.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

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

Sep 12, 2023

The c.1460G>C (p.R487T) alteration is located in exon 12 (coding exon 11) of the RBM25 gene. This alteration results from a G to C substitution at nucleotide position 1460, causing the arginine (R) at amino acid position 487 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

Uncertain

0.51

BayesDel_addAF

Uncertain

0.063

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;T

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.94

.;D

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.50

D;D

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.20

Sift

Benign

0.20

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.98

D;D

Vest4

0.61

MutPred

0.47

Gain of phosphorylation at R487 (P = 0.0051);Gain of phosphorylation at R487 (P = 0.0051);

MVP

0.41

MPC

1.8

ClinPred

0.82

GERP RS

5.7

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.8

Varity_R

0.37

gMVP

0.49

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.

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