rs2295682

Positions:

• chr14-22905653-C-A
• chr14-22905653-C-G
• chr14-22905653-C-T

Variant summary

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

The NM_001077351.2(RBM23):​c.408G>T​(p.Arg136Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM23 NM_001077351.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.943

Genes affected

RBM23 (HGNC:20155): (RNA binding motif protein 23) This gene encodes a member of the U2AF-like family of RNA binding proteins. This protein interacts with some steroid nuclear receptors, localizes to the promoter of a steroid- responsive gene, and increases transcription of steroid-responsive transcriptional reporters in a hormone-dependent manner. It is also implicated in the steroid receptor-dependent regulation of alternative splicing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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=0.09481859).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM23	NM_001077351.2	c.408G>T	p.Arg136Ser	missense_variant	6/14	ENST00000359890.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM23	ENST00000359890.8	c.408G>T	p.Arg136Ser	missense_variant	6/14	1	NM_001077351.2	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	8.1
DANN	Benign	0.69
DEOGEN2	Benign	0.0094	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.095	T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.094
Sift	Uncertain	0.021	D;D
Sift4G	Uncertain	0.025	D;D
Polyphen		0.10	B;B
Vest4		0.17
MutPred		0.48		Gain of catalytic residue at K141 (P = 0);.;
MVP		0.57
MPC		0.18
ClinPred		0.23	T
GERP RS		-0.14
Varity_R		0.093
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2295682; hg19: chr14-23374862;