Genetic Variant RBM26:p.Leu787Phe (chr13-79342730-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS2

The NM_001366735.2(RBM26):c.2361G>C(p.Leu787Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000033 in 151,720 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Consequence

RBM26
NM_001366735.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.259

Variant links:

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]

RBM26 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM26	NM_001366735.2 link	c.2361G>C	p.Leu787Phe	missense_variant	Exon 17 of 22	ENST00000438737.3	NP_001353664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RBM26	ENST00000438737.3 link	c.2361G>C	p.Leu787Phe	missense_variant	Exon 17 of 22	5	NM_001366735.2	ENSP00000387531.2	Q5T8P6-1
RBM26	ENST00000438724.5 link	c.2289G>C	p.Leu763Phe	missense_variant	Exon 16 of 21	1		ENSP00000390222.1	Q5T8P6-2
RBM26	ENST00000267229.11 link	c.2280G>C	p.Leu760Phe	missense_variant	Exon 16 of 21	1		ENSP00000267229.7	Q5T8P6-3
RBM26	ENST00000622611.4 link	c.2367G>C	p.Leu789Phe	missense_variant	Exon 17 of 22	2		ENSP00000483408.1	A0A087X0H9

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151720

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250976

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135692

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151720

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74128

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2280G>C (p.L760F) alteration is located in exon 16 (coding exon 16) of the RBM26 gene. This alteration results from a G to C substitution at nucleotide position 2280, causing the leucine (L) at amino acid position 760 to be replaced by a phenylalanine (F). 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

0.69

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

.;.;.;T

Eigen

Benign

0.0056

Eigen_PC

Benign

-0.099

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.97

D;D;D;D

M_CAP

Benign

0.067

MetaRNN

Uncertain

0.63

D;D;D;D

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.6

.;.;.;M

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.9

D;.;D;.

REVEL

Uncertain

0.33

Sift

Uncertain

0.0020

D;.;D;.

Sift4G

Uncertain

0.0090

D;D;D;D

Polyphen

1.0

D;.;D;D

Vest4

0.74

MutPred

0.41

.;.;.;Gain of methylation at K786 (P = 0.0272);

MVP

0.34

MPC

1.4

ClinPred

0.94

GERP RS

-1.7

Varity_R

0.49

gMVP

0.37

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over