1-110340412-A-G
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_022768.5(RBM15):āc.1007A>Gā(p.Tyr336Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,614,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000079 ( 0 hom., cov: 32)
Exomes š: 0.000027 ( 0 hom. )
Consequence
RBM15
NM_022768.5 missense
NM_022768.5 missense
Scores
1
11
7
Clinical Significance
Conservation
PhyloP100: 2.62
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.21886674).
BS2
High AC in GnomAd4 at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RBM15 | NM_022768.5 | c.1007A>G | p.Tyr336Cys | missense_variant | 1/3 | ENST00000369784.9 | NP_073605.4 | |
RBM15 | NM_001201545.2 | c.1007A>G | p.Tyr336Cys | missense_variant | 1/2 | NP_001188474.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RBM15 | ENST00000369784.9 | c.1007A>G | p.Tyr336Cys | missense_variant | 1/3 | 1 | NM_022768.5 | ENSP00000358799 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000788 AC: 12AN: 152204Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251256Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135898
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GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461890Hom.: 0 Cov.: 37 AF XY: 0.0000289 AC XY: 21AN XY: 727244
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GnomAD4 genome AF: 0.0000788 AC: 12AN: 152322Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74482
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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 | Mar 19, 2024 | The c.1007A>G (p.Y336C) alteration is located in exon 1 (coding exon 1) of the RBM15 gene. This alteration results from a A to G substitution at nucleotide position 1007, causing the tyrosine (Y) at amino acid position 336 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;.;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.;.;.
REVEL
Benign
Sift
Uncertain
D;.;.;.;.
Sift4G
Uncertain
T;T;T;T;T
Polyphen
D;.;D;D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at