14-22904984-G-C

Position:

• chr14-22904984-G-C

Variant summary

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

The NM_001077351.2(RBM23):​c.755C>G​(p.Ala252Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM23 NM_001077351.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.46

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM23	NM_001077351.2	c.755C>G	p.Ala252Gly	missense_variant	9/14	ENST00000359890.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM23	ENST00000359890.8	c.755C>G	p.Ala252Gly	missense_variant	9/14	1	NM_001077351.2	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2023

The c.755C>G (p.A252G) alteration is located in exon 9 (coding exon 8) of the RBM23 gene. This alteration results from a C to G substitution at nucleotide position 755, causing the alanine (A) at amino acid position 252 to be replaced by a glycine (G). 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	Uncertain	0.34
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T;.;.;.;T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.47	T;T;T;T;T;T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Benign	1.4	L;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.7	N;N;N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.040	D;D;D;D;D;D
Sift4G	Uncertain	0.060	T;D;T;T;T;.
Polyphen		0.76	P;.;B;B;.;.
Vest4		0.46
MutPred		0.38		Gain of catalytic residue at N253 (P = 0.0601);.;.;.;.;.;
MVP		0.84
MPC		0.11
ClinPred		0.81	D
GERP RS		5.8
Varity_R		0.15
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-23374193;