13-79320677-G-C

Position:

• chr13-79320677-G-C

Variant summary

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

The NM_001366735.2(RBM26):​c.2968C>G​(p.Leu990Val) variant causes a missense change. 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: 29)
• Consequence: RBM26 NM_001366735.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.70

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23592854).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM26	NM_001366735.2	c.2968C>G	p.Leu990Val	missense_variant	22/22	ENST00000438737.3	NP_001353664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM26	ENST00000438737.3	c.2968C>G	p.Leu990Val	missense_variant	22/22	5	NM_001366735.2	ENSP00000387531.2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 29

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 27, 2023

The c.2887C>G (p.L963V) alteration is located in exon 21 (coding exon 21) of the RBM26 gene. This alteration results from a C to G substitution at nucleotide position 2887, causing the leucine (L) at amino acid position 963 to be replaced by a valine (V). 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	Pathogenic	0.57
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.040	.;.;.;T
Eigen	Uncertain	0.63
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	.;.;.;M
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.4	N;.;N;N
REVEL	Benign	0.17
Sift	Benign	0.32	T;.;T;D
Sift4G	Uncertain	0.059	T;T;T;T
Polyphen		0.97	D;.;D;P
Vest4		0.27
MutPred		0.14		.;.;.;Loss of helix (P = 0.2271);
MVP		0.48
MPC		0.46
ClinPred		0.70	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.24

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: chr13-79894812;