1-110340024-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22382653).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022768.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM15	NM_022768.5	MANE Select	c.619C>G	p.Leu207Val	missense	Exon 1 of 3	NP_073605.4
	RBM15	NM_001201545.2		c.619C>G	p.Leu207Val	missense	Exon 1 of 2	NP_001188474.1	Q96T37-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM15	ENST00000369784.9	TSL:1 MANE Select	c.619C>G	p.Leu207Val	missense	Exon 1 of 3	ENSP00000358799.3	Q96T37-1
	RBM15	ENST00000618772.4	TSL:1	c.619C>G	p.Leu207Val	missense	Exon 1 of 3	ENSP00000483133.1	Q96T37-1
	RBM15	ENST00000487146.8	TSL:1	c.619C>G	p.Leu207Val	missense	Exon 1 of 2	ENSP00000473552.3	Q96T37-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		3.3
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.14
Sift	Benign	0.096	T
Sift4G	Benign	0.63	T
Polyphen		0.99	D
Vest4		0.33
MutPred		0.20		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
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

hg19: chr1-110882646;