1-110340024-C-G

Variant names:

• chr1-110340024-C-G
• NM_022768.5:c.619C>G

Variant summary

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

The NM_022768.5(RBM15):​c.619C>G​(p.Leu207Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM15 NM_022768.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.26

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=0.22382653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM15	NM_022768.5	c.619C>G	p.Leu207Val	missense_variant	Exon 1 of 3	ENST00000369784.9	NP_073605.4
RBM15	NM_001201545.2	c.619C>G	p.Leu207Val	missense_variant	Exon 1 of 2		NP_001188474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM15	ENST00000369784.9	c.619C>G	p.Leu207Val	missense_variant	Exon 1 of 3	1	NM_022768.5	ENSP00000358799.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.619C>G (p.L207V) 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 619, causing the leucine (L) at amino acid position 207 to be replaced by a valine (V). 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	0.076
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.099	T;.;.;T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.77	.;T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.22	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;L;L;L;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.22	N;.;.;.;.
REVEL	Benign	0.14
Sift	Benign	0.096	T;.;.;.;.
Sift4G	Benign	0.63	T;T;T;T;T
Polyphen		0.99	D;.;P;D;.
Vest4		0.33
MutPred		0.20		Gain of methylation at K203 (P = 0.0772);Gain of methylation at K203 (P = 0.0772);Gain of methylation at K203 (P = 0.0772);Gain of methylation at K203 (P = 0.0772);.;
MVP		0.38
MPC		1.6
ClinPred		0.72	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-110882646;