Variant X-48576410-T-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.307T>C(p.Tyr103His) variant causes a missense change. The variant allele was found at a frequency of 0.000000912 in 1,096,385 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: not found (cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

RBM3
NM_006743.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.40

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:

Genome browser will be placed here

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=0.27050817).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM3	NM_006743.5 linkuse as main transcript	c.307T>C	p.Tyr103His	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.307T>C	p.Tyr103His	missense_variant	4/7	1	NM_006743.5	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000563

AC:

AN:

177603

Hom.:

AF XY:

0.0000160

AC XY:

AN XY:

62541

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000227

GnomAD4 exome

AF:

9.12e-7

AC:

AN:

1096385

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

361851

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000286

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:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

May 18, 2022

The c.307T>C (p.Y103H) alteration is located in exon 4 (coding exon 3) of the RBM3 gene. This alteration results from a T to C substitution at nucleotide position 307, causing the tyrosine (Y) at amino acid position 103 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.37

Cadd

Benign

Dann

Benign

0.95

DEOGEN2

Benign

0.26

T;T

FATHMM_MKL

Uncertain

0.89

M_CAP

Benign

0.048

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

0.91

D;D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.23

Sift

Benign

0.52

T;T

Sift4G

Benign

0.079

T;T

Polyphen

0.94

P;P

Vest4

0.25

MVP

0.88

MPC

1.9

ClinPred

0.51

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.65

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