Variant 13-79354483-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001366735.2(RBM26):c.1942A>G(p.Ile648Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000318 in 1,605,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

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

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

RBM26
NM_001366735.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.315

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014159024).

BP6

Variant 13-79354483-T-C is Benign according to our data. Variant chr13-79354483-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3152279.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM26	NM_001366735.2 link	c.1942A>G	p.Ile648Val	missense_variant	13/22	ENST00000438737.3	NP_001353664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RBM26	ENST00000438737.3 link	c.1942A>G	p.Ile648Val	missense_variant	13/22	5	NM_001366735.2	ENSP00000387531.2	Q5T8P6-1
RBM26	ENST00000438724.5 link	c.1942A>G	p.Ile648Val	missense_variant	13/21	1		ENSP00000390222.1	Q5T8P6-2
RBM26	ENST00000267229.11 link	c.1933A>G	p.Ile645Val	missense_variant	13/21	1		ENSP00000267229.7	Q5T8P6-3
RBM26	ENST00000622611.4 link	c.1948A>G	p.Ile650Val	missense_variant	13/22	2		ENSP00000483408.1	A0A087X0H9

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000600

AC:

AN:

250090

Hom.:

AF XY:

0.0000888

AC XY:

AN XY:

135208

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000531

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000316

AC:

AN:

1453450

Hom.:

Cov.:

AF XY:

0.0000443

AC XY:

AN XY:

723022

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.0000673

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000200

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000172

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000722

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.021

DANN

Benign

0.44

DEOGEN2

Benign

0.010

.;.;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.014

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.14

N;.;.;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.40

N;.;N;.

REVEL

Benign

0.10

Sift

Benign

0.58

T;.;T;.

Sift4G

Benign

0.38

T;T;T;T

Polyphen

0.0040

B;.;B;B

Vest4

0.093

MutPred

0.20

Loss of helix (P = 0.0041);.;.;Loss of helix (P = 0.0041);

MVP

0.22

MPC

0.39

ClinPred

0.0059

GERP RS

-11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.029

gMVP

0.11

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