Variant X-48575221-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006743.5(RBM3):c.41A>G(p.Asn14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000828 in 1,208,417 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000073 ( 0 hom. 3 hem. )

Consequence

RBM3
NM_006743.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.65

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:

RBM3 (HGNC:):

RBM3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13731211).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM3	NM_006743.5 linkuse as main transcript	c.41A>G	p.Asn14Ser	missense_variant	2/7	ENST00000376759.8	NP_006734.1	P98179A0A024QYX3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM3	ENST00000376759.8 linkuse as main transcript	c.41A>G	p.Asn14Ser	missense_variant	2/7	1	NM_006743.5	ENSP00000365950.3		P98179

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

111135

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33331

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000963

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:

0.000676

GnomAD4 exome

AF:

0.00000729

AC:

AN:

1097282

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

362700

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000285

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:

0.00000594

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000180

AC:

AN:

111135

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33331

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000963

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:

0.000676

Bravo

AF:

0.0000189

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

Nov 08, 2024

The c.41A>G (p.N14S) alteration is located in exon 2 (coding exon 1) of the RBM3 gene. This alteration results from a A to G substitution at nucleotide position 41, causing the asparagine (N) at amino acid position 14 to be replaced by a serine (S). 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

0.10

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.10

T;T

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.97

.;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

-1.4

N;N

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.16

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.17

B;B

Vest4

0.092

MutPred

0.45

Gain of disorder (P = 0.0497);Gain of disorder (P = 0.0497);

MVP

0.89

MPC

0.74

ClinPred

0.63

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.093

gMVP

0.71

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