1-110339562-G-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_022768.5(RBM15):c.157G>C(p.Val53Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000517 in 1,605,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000028 ( 0 hom. )
Consequence
RBM15
NM_022768.5 missense
NM_022768.5 missense
Scores
1
2
15
Clinical Significance
Conservation
PhyloP100: 4.32
Genes affected
RBM15 (HGNC:14959): (RNA binding motif protein 15) Members of the SPEN (Split-end) family of proteins, including RBM15, 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=0.02825132).
BS2
?
High AC in GnomAd at 42 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBM15 | NM_022768.5 | c.157G>C | p.Val53Leu | missense_variant | 1/3 | ENST00000369784.9 | |
RBM15 | NM_001201545.2 | c.157G>C | p.Val53Leu | missense_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBM15 | ENST00000369784.9 | c.157G>C | p.Val53Leu | missense_variant | 1/3 | 1 | NM_022768.5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000276 AC: 42AN: 152258Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
42
AN:
152258
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000762 AC: 19AN: 249264Hom.: 0 AF XY: 0.0000518 AC XY: 7AN XY: 135142
GnomAD3 exomes
AF:
AC:
19
AN:
249264
Hom.:
AF XY:
AC XY:
7
AN XY:
135142
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000282 AC: 41AN: 1453378Hom.: 0 Cov.: 30 AF XY: 0.0000222 AC XY: 16AN XY: 721188
GnomAD4 exome
AF:
AC:
41
AN:
1453378
Hom.:
Cov.:
30
AF XY:
AC XY:
16
AN XY:
721188
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000276 AC: 42AN: 152258Hom.: 0 Cov.: 33 AF XY: 0.000269 AC XY: 20AN XY: 74382
GnomAD4 genome
?
AF:
AC:
42
AN:
152258
Hom.:
Cov.:
33
AF XY:
AC XY:
20
AN XY:
74382
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
4
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
10
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 | Jun 16, 2023 | The c.157G>C (p.V53L) alteration is located in exon 1 (coding exon 1) of the RBM15 gene. This alteration results from a G to C substitution at nucleotide position 157, causing the valine (V) at amino acid position 53 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;N;.
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.;.;.
REVEL
Benign
Sift
Benign
D;.;.;.;.
Sift4G
Benign
T;T;T;T;T
Polyphen
B;.;B;B;.
Vest4
MutPred
Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at