1-235138112-G-A

Position:

chr1-235138112-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000408888.8(RBM34):c.764C>T(p.Ala255Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,609,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

RBM34
ENST00000408888.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.60

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 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=0.20935336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM34	NM_015014.4 linkuse as main transcript	c.764C>T	p.Ala255Val	missense_variant	7/11	ENST00000408888.8	NP_055829.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM34	ENST00000408888.8 linkuse as main transcript	c.764C>T	p.Ala255Val	missense_variant	7/11	1	NM_015014.4	ENSP00000386226	P1	P42696-1
RBM34	ENST00000447801.5 linkuse as main transcript	c.698C>T	p.Ala233Val	missense_variant	6/10	5		ENSP00000400000
RBM34	ENST00000474086.5 linkuse as main transcript	c.*375C>T		3_prime_UTR_variant, NMD_transcript_variant	6/9	2		ENSP00000420236
ARID4B	ENST00000474953.5 linkuse as main transcript	c.*766C>T		3_prime_UTR_variant, NMD_transcript_variant	13/17	2		ENSP00000420620

Frequencies

GnomAD3 genomes

AF:

0.0000857

AC:

AN:

151622

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000315

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:

0.0000283

AC:

AN:

247112

Hom.:

AF XY:

0.0000373

AC XY:

AN XY:

133916

show subpopulations

Gnomad AFR exome

AF:

0.000389

Gnomad AMR exome

AF:

0.0000294

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

AF:

0.00000686

AC:

AN:

1458226

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725296

show subpopulations

Gnomad4 AFR exome

AF:

0.000271

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000857

AC:

AN:

151622

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74016

show subpopulations

Gnomad4 AFR

AF:

0.000315

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

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.000531

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.764C>T (p.A255V) alteration is located in exon 7 (coding exon 7) of the RBM34 gene. This alteration results from a C to T substitution at nucleotide position 764, causing the alanine (A) at amino acid position 255 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

Benign

0.24

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

T;T

Eigen

Benign

-0.088

Eigen_PC

Benign

-0.075

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.041

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

0.84

N;N

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.24

Sift

Uncertain

0.027

D;D

Sift4G

Benign

0.066

T;T

Polyphen

0.55

P;.

Vest4

0.43

MVP

0.84

MPC

0.29

ClinPred

0.16

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.082

gMVP

0.47

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