Variant 14-73110867-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000261973.12(RBM25):c.1729A>C(p.Ile577Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,459,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

RBM25
ENST00000261973.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.42

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08360347).

BS2

High AC in GnomAdExome4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM25	NM_021239.3 linkuse as main transcript	c.1729A>C	p.Ile577Leu	missense_variant	15/19	ENST00000261973.12	NP_067062.1	P49756-1
RBM25	XM_011537044.4 linkuse as main transcript	c.1729A>C	p.Ile577Leu	missense_variant	16/20		XP_011535346.1	P49756-1
RBM25	XM_047431641.1 linkuse as main transcript	c.1729A>C	p.Ile577Leu	missense_variant	15/16		XP_047287597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM25	ENST00000261973.12 linkuse as main transcript	c.1729A>C	p.Ile577Leu	missense_variant	15/19	1	NM_021239.3	ENSP00000261973.7		P49756-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249164

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1459650

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000227

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Nov 10, 2022

The c.1729A>C (p.I577L) alteration is located in exon 15 (coding exon 14) of the RBM25 gene. This alteration results from a A to C substitution at nucleotide position 1729, causing the isoleucine (I) at amino acid position 577 to be replaced by a leucine (L). 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

0.071

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.048

T;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.067

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.85

.;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.084

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.41

N;N

MutationTaster

Benign

0.74

D;D

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.23

N;N

REVEL

Benign

0.12

Sift

Benign

0.87

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.0010

B;B

Vest4

0.40

MutPred

0.18

Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);

MVP

0.17

MPC

0.48

ClinPred

0.092

GERP RS

5.4

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.13

gMVP

0.043

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