3-51391739-C-T

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

1
17

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]

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
RBM15BNM_013286.5 linkc.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
RBM15BENST00000563281.2 linkc.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:
82
AN:
151762
Hom.:
2
Cov.:
32
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:
52
AN:
154240
Hom.:
0
AF XY:
0.000315
AC XY:
28
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.:
0
Cov.:
32
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:
82
AN:
151872
Hom.:
2
Cov.:
32
AF XY:
0.000633
AC XY:
47
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.:
0
Bravo
AF:
0.000567
ExAC
AF:
0.000330
AC:
37

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
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
20
DANN
Benign
0.97
DEOGEN2
Benign
0.025
T
Eigen
Benign
-0.99
Eigen_PC
Benign
-0.94
FATHMM_MKL
Benign
0.026
N
LIST_S2
Benign
0.51
T
M_CAP
Benign
0.046
D
MetaRNN
Benign
0.0049
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
-0.34
N
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
0.030
N
Sift
Benign
0.25
T
Sift4G
Benign
0.85
T
Polyphen
0.0010
B
Vest4
0.18
MVP
0.10
ClinPred
0.030
T
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.

Other links and lift over

dbSNP: rs538902846; hg19: chr3-51429170; API