1-235131741-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015014.4(RBM34):c.1265G>A(p.Arg422His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000393 in 1,602,232 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

RBM34
NM_015014.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.99

Variant links:

Genes affected

RBM34 (HGNC:28965): (RNA binding motif protein 34) This gene encodes a member of the RNA-binding motif family of RNA recognition motif proteins. The encoded protein contains an RNA-binding domain made up of two RNA recognition motif subdomains referred to as RNA recognition motif-1 and RNA recognition motif-2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

RBM34 links:

ARID4B (HGNC:15550): (AT-rich interaction domain 4B) This gene encodes a protein with sequence similarity to retinoblastoma-binding protein-1. The encoded protein is a subunit of the histone deacetylase-dependant SIN3A transcriptional corepressor complex, which functions in diverse cellular processes including proliferation, differentiation, apoptosis, oncogenesis, and cell fate determination. The gene product is recognized by IgG antibody isolated from a breast cancer patient and appears to be a molecular marker associated with a broad range of human malignancies. Alternate transcriptional splice variants encoding different isoforms have been characterized. [provided by RefSeq, Jul 2008]

ARID4B 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;

BP4

Computational evidence support a benign effect (MetaRNN=0.041348666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM34	NM_015014.4 link	c.1265G>A	p.Arg422His	missense_variant	Exon 11 of 11	ENST00000408888.8	NP_055829.2	P42696-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM34	ENST00000408888.8 link	c.1265G>A	p.Arg422His	missense_variant	Exon 11 of 11	1	NM_015014.4	ENSP00000386226.3		P42696-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000375

AC:

AN:

240056

Hom.:

AF XY:

0.0000230

AC XY:

AN XY:

130448

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000125

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000414

AC:

AN:

1449952

Hom.:

Cov.:

AF XY:

0.0000430

AC XY:

AN XY:

720846

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000481

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000143

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000397

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000331

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1265G>A (p.R422H) alteration is located in exon 11 (coding exon 11) of the RBM34 gene. This alteration results from a G to A substitution at nucleotide position 1265, causing the arginine (R) at amino acid position 422 to be replaced by a histidine (H). 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

Benign

0.073

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.0040

DANN

Benign

0.55

DEOGEN2

Benign

0.048

T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.27

T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.041

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.92

L;.

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.073

Sift

Benign

0.61

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.0

B;.

Vest4

0.048

MutPred

0.23

Gain of glycosylation at K424 (P = 0.0785);.;

MVP

0.24

MPC

0.085

ClinPred

0.017

GERP RS

-11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.015

gMVP

0.21

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