rs1553224979

Variant names:

• chr1-110341317-C-A
• rs1553224979
• NM_022768.5:c.1912C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-110341317-C-A
• chr1-110341317-C-G
• chr1-110341317-C-T

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.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. 15/22 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
• 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=0.08703801).

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.1912C>A	p.Gln638Lys	missense	Exon 1 of 3	NP_073605.4
	RBM15	NM_001201545.2		c.1912C>A	p.Gln638Lys	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.1912C>A	p.Gln638Lys	missense	Exon 1 of 3	ENSP00000358799.3	Q96T37-1
	RBM15	ENST00000618772.4	TSL:1	c.1912C>A	p.Gln638Lys	missense	Exon 1 of 3	ENSP00000483133.1	Q96T37-1
	RBM15	ENST00000487146.8	TSL:1	c.1912C>A	p.Gln638Lys	missense	Exon 1 of 2	ENSP00000473552.3	Q96T37-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: other

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Neuroblastoma (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.13
Eigen_PC	Benign	0.042
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.4
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.048
Sift	Benign	0.47	T
Sift4G	Benign	0.50	T
Polyphen		0.039	B
Vest4		0.13
MutPred		0.28		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
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

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