chr3-51391624-C-A

Variant summary

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

The NM_013286.5(RBM15B):​c.225C>A​(p.Asp75Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000244 in 1,186,568 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

RBM15B
NM_013286.5 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.222
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.071320325).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RBM15BNM_013286.5 linkc.225C>A p.Asp75Glu 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.225C>A p.Asp75Glu missense_variant Exon 1 of 1 6 NM_013286.5 ENSP00000454545.1 Q8NDT2-1

Frequencies

GnomAD3 genomes
AF:
0.0000333
AC:
5
AN:
150024
Hom.:
0
Cov.:
32
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:
0.0000744
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000232
AC:
24
AN:
1036544
Hom.:
0
Cov.:
31
AF XY:
0.0000286
AC XY:
14
AN XY:
488824
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000521
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000258
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000333
AC:
5
AN:
150024
Hom.:
0
Cov.:
32
AF XY:
0.0000137
AC XY:
1
AN XY:
73186
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:
0.0000744
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000540
Hom.:
0
Bravo
AF:
0.0000340

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 05, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.225C>A (p.D75E) alteration is located in exon 1 (coding exon 1) of the RBM15B gene. This alteration results from a C to A substitution at nucleotide position 225, causing the aspartic acid (D) at amino acid position 75 to be replaced by a glutamic acid (E). 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
0.12
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
17
DANN
Benign
0.92
DEOGEN2
Benign
0.026
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.37
T
M_CAP
Benign
0.055
D
MetaRNN
Benign
0.071
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.34
N
PrimateAI
Pathogenic
0.94
D
PROVEAN
Benign
-0.24
N
Sift
Benign
0.036
D
Sift4G
Benign
1.0
T
Polyphen
0.0010
B
Vest4
0.11
MutPred
0.25
Gain of sheet (P = 0.0507);
MVP
0.17
ClinPred
0.080
T
GERP RS
1.6
Varity_R
0.056
gMVP
0.11

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: rs1164640309; hg19: chr3-51429055; API