rs1553224979

chr1-110341317-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022768.5(RBM15):c.1912C>A(p.Gln638Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM15 NM_022768.5 missense
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: 1.44

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08703801).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM15	NM_022768.5	c.1912C>A	p.Gln638Lys	missense_variant	1/3	ENST00000369784.9
RBM15	NM_001201545.2	c.1912C>A	p.Gln638Lys	missense_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM15	ENST00000369784.9	c.1912C>A	p.Gln638Lys	missense_variant	1/3	1	NM_022768.5	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: other

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Neuroblastoma Other:1

other, no assertion criteria provided

clinical testing

Donald Williams Parsons Laboratory, Baylor College of Medicine

May 01, 2016

- 3: Mutations in other consensus cancer genes, not currently considered targetable

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	21
Dann	Benign	0.95
DEOGEN2	Benign	0.28	T;.;.;T;.
Eigen	Benign	-0.13
Eigen_PC	Benign	0.042
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.087	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L;L;L;.
MutationTaster	Benign	0.97	D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.71	N;.;.;.;.
REVEL	Benign	0.048
Sift	Benign	0.47	T;.;.;.;.
Sift4G	Benign	0.50	T;T;T;T;T
Polyphen		0.039	B;.;B;B;.
Vest4		0.13
MutPred		0.28		Gain of ubiquitination at Q638 (P = 0.0131);Gain of ubiquitination at Q638 (P = 0.0131);Gain of ubiquitination at Q638 (P = 0.0131);Gain of ubiquitination at Q638 (P = 0.0131);.;
MVP		0.34
MPC		0.92
ClinPred		0.17	T
GERP RS		4.8
Varity_R		0.25
gMVP		0.32

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

Other links and lift over

dbSNP: rs1553224979; hg19: chr1-110883939; COSMIC: COSV63924155; COSMIC: COSV63924155;