13-79344253-G-C

Position:

• chr13-79344253-G-C

Variant summary

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

The NM_001366735.2(RBM26):​c.2254C>G​(p.Gln752Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM26 NM_001366735.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.85

Genes affected

RBM26 (HGNC:20327): (RNA binding motif protein 26) Enables RNA binding activity. Predicted to be involved in mRNA processing. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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	Protein	UniProt
RBM26	NM_001366735.2	c.2254C>G	p.Gln752Glu	missense_variant	16/22	ENST00000438737.3	NP_001353664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM26	ENST00000438737.3	c.2254C>G	p.Gln752Glu	missense_variant	16/22	5	NM_001366735.2	ENSP00000387531.2
RBM26	ENST00000438724.5	c.2182C>G	p.Gln728Glu	missense_variant	15/21	1		ENSP00000390222.1
RBM26	ENST00000267229.11	c.2173C>G	p.Gln725Glu	missense_variant	15/21	1		ENSP00000267229.7
RBM26	ENST00000622611.4	c.2260C>G	p.Gln754Glu	missense_variant	16/22	2		ENSP00000483408.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Jul 10, 2024

The c.2173C>G (p.Q725E) alteration is located in exon 15 (coding exon 15) of the RBM26 gene. This alteration results from a C to G substitution at nucleotide position 2173, causing the glutamine (Q) at amino acid position 725 to be replaced by a glutamic acid (E). 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	0.49
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	.;.;.;D
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Uncertain	0.27	D
MetaRNN	Uncertain	0.71	D;D;D;D
MetaSVM	Uncertain	0.44	D
MutationAssessor	Uncertain	2.6	.;.;.;M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-2.4	N;.;N;.
REVEL	Uncertain	0.64
Sift	Uncertain	0.019	D;.;D;.
Sift4G	Benign	0.089	T;T;T;T
Polyphen		0.79	P;.;P;P
Vest4		0.74
MutPred		0.34		.;.;.;Gain of ubiquitination at K747 (P = 0.0259);
MVP		0.92
MPC		1.2
ClinPred		0.98	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.69

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: chr13-79918388;