Variant X-48576387-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006743.5(RBM3):c.284G>C(p.Gly95Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000414 in 1,209,087 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Consequence

RBM3
NM_006743.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.74

Variant links:

Genes affected

RBM3 (HGNC:9900): (RNA binding motif protein 3) This gene is a member of the glycine-rich RNA-binding protein family and encodes a protein with one RNA recognition motif (RRM) domain. Expression of this gene is induced by cold shock and low oxygen tension. A pseudogene exists on chromosome 1. Multiple alternatively spliced transcript variants that are predicted to encode different isoforms have been characterized although some of these variants fit nonsense-mediated decay (NMD) criteria. [provided by RefSeq, Jul 2008]

RBM3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31640998).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM3	NM_006743.5 linkuse as main transcript	c.284G>C	p.Gly95Ala	missense_variant	4/7	ENST00000376759.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM3	ENST00000376759.8 linkuse as main transcript	c.284G>C	p.Gly95Ala	missense_variant	4/7	1	NM_006743.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111820

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33992

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000955

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000273

AC:

AN:

1097267

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362669

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000356

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111820

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33992

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000955

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

Mar 31, 2023

The c.284G>C (p.G95A) alteration is located in exon 4 (coding exon 3) of the RBM3 gene. This alteration results from a G to C substitution at nucleotide position 284, causing the glycine (G) at amino acid position 95 to be replaced by an alanine (A). 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

0.18

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Benign

-0.29

Cadd

Uncertain

Dann

Benign

0.96

DEOGEN2

Benign

0.25

T;T

FATHMM_MKL

Uncertain

0.91

M_CAP

Benign

0.0082

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.7

M;M

MutationTaster

Benign

0.99

D;D;N;N

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.6

D;D

REVEL

Uncertain

0.32

Sift

Benign

0.34

T;T

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.86

P;P

Vest4

0.47

MutPred

0.40

Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);

MVP

0.94

MPC

1.7

ClinPred

0.64

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.21

gMVP

0.76

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