Genetic Variant RBM15B:p.Pro114Ser (chr3-51391739-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_013286.5(RBM15B):c.340C>T(p.Pro114Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000538 in 1,532,860 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 0 hom. )

Consequence

RBM15B
NM_013286.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42

Variant links:

Genes affected

RBM15B (HGNC:24303): (RNA binding motif protein 15B) Members of the SPEN (Split-end) family of proteins, including RBM15B, have repressor function in several signaling pathways and may bind to RNA through interaction with spliceosome components (Hiriart et al., 2005 [PubMed 16129689]).[supplied by OMIM, Feb 2009]

RBM15B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004914254).

BS2

High AC in GnomAd4 at 82 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM15B	NM_013286.5 link	c.340C>T	p.Pro114Ser	missense_variant	Exon 1 of 1	ENST00000563281.2	NP_037418.3	Q8NDT2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM15B	ENST00000563281.2 link	c.340C>T	p.Pro114Ser	missense_variant	Exon 1 of 1	6	NM_013286.5	ENSP00000454545.1		Q8NDT2-1

Frequencies

GnomAD3 genomes

AF:

0.000540

AC:

AN:

151762

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.0319

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000648

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000337

AC:

AN:

154240

Hom.:

AF XY:

0.000315

AC XY:

AN XY:

89002

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000165

Gnomad ASJ exome

AF:

0.000139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000172

Gnomad FIN exome

AF:

0.000108

Gnomad NFE exome

AF:

0.000595

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000538

AC:

743

AN:

1380988

Hom.:

Cov.:

AF XY:

0.000544

AC XY:

373

AN XY:

685766

show subpopulations

Gnomad4 AFR exome

AF:

0.000141

Gnomad4 AMR exome

AF:

0.000169

Gnomad4 ASJ exome

AF:

0.0000419

Gnomad4 EAS exome

AF:

0.0000307

Gnomad4 SAS exome

AF:

0.000227

Gnomad4 FIN exome

AF:

0.0000276

Gnomad4 NFE exome

AF:

0.000630

Gnomad4 OTH exome

AF:

0.000508

GnomAD4 genome

AF:

0.000540

AC:

AN:

151872

Hom.:

Cov.:

AF XY:

0.000633

AC XY:

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000648

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000624

Hom.:

Bravo

AF:

0.000567

ExAC

AF:

0.000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.340C>T (p.P114S) alteration is located in exon 1 (coding exon 1) of the RBM15B gene. This alteration results from a C to T substitution at nucleotide position 340, causing the proline (P) at amino acid position 114 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

0.065

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.025

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.51

M_CAP

Benign

0.046

MetaRNN

Benign

0.0049

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.34

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

0.030

Sift

Benign

0.25

Sift4G

Benign

0.85

Polyphen

0.0010

Vest4

0.18

MVP

0.10

ClinPred

0.030

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.4

Varity_R

0.061

gMVP

0.31

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