1-110339831-C-G

Variant summary

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

The NM_022768.5(RBM15):ā€‹c.426C>Gā€‹(p.Ser142Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000938 in 1,599,188 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000090 ( 0 hom. )

Consequence

RBM15
NM_022768.5 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.01
Variant links:
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.15721208).
BS2
High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RBM15NM_022768.5 linkuse as main transcriptc.426C>G p.Ser142Arg missense_variant 1/3 ENST00000369784.9 NP_073605.4
RBM15NM_001201545.2 linkuse as main transcriptc.426C>G p.Ser142Arg missense_variant 1/2 NP_001188474.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RBM15ENST00000369784.9 linkuse as main transcriptc.426C>G p.Ser142Arg missense_variant 1/31 NM_022768.5 ENSP00000358799 A2Q96T37-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152158
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000824
AC:
2
AN:
242782
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
132314
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000183
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000898
AC:
13
AN:
1447030
Hom.:
0
Cov.:
37
AF XY:
0.00000976
AC XY:
7
AN XY:
717346
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000118
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152158
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsDec 23, 2022The c.426C>G (p.S142R) alteration is located in exon 1 (coding exon 1) of the RBM15 gene. This alteration results from a C to G substitution at nucleotide position 426, causing the serine (S) at amino acid position 142 to be replaced by an arginine (R). 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
Uncertain
0.53
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T;.;.;T;.
Eigen
Benign
0.074
Eigen_PC
Benign
0.17
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.80
.;T;T;T;T
M_CAP
Benign
0.0085
T
MetaRNN
Benign
0.16
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
L;L;L;L;.
MutationTaster
Benign
0.95
D
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-0.41
N;.;.;.;.
REVEL
Benign
0.043
Sift
Benign
0.047
D;.;.;.;.
Sift4G
Benign
0.36
T;T;T;T;T
Polyphen
0.74
P;.;P;P;.
Vest4
0.21
MutPred
0.38
Loss of phosphorylation at S142 (P = 3e-04);Loss of phosphorylation at S142 (P = 3e-04);Loss of phosphorylation at S142 (P = 3e-04);Loss of phosphorylation at S142 (P = 3e-04);.;
MVP
0.31
MPC
0.80
ClinPred
0.42
T
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.9
Varity_R
0.38
gMVP
0.57

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: rs781645412; hg19: chr1-110882453; API