Variant 3-29868868-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001003793.3(RBMS3):c.648G>T(p.Glu216Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RBMS3
NM_001003793.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.36

Variant links:

Genes affected

RBMS3 (HGNC:13427): (RNA binding motif single stranded interacting protein 3) This gene encodes an RNA-binding protein that belongs to the c-myc gene single-strand binding protein family. These proteins are characterized by the presence of two sets of ribonucleoprotein consensus sequence (RNP-CS) that contain conserved motifs, RNP1 and RNP2, originally described in RNA binding proteins, and required for DNA binding. These proteins have been implicated in such diverse functions as DNA replication, gene transcription, cell cycle progression and apoptosis. The encoded protein was isolated by virtue of its binding to an upstream element of the alpha2(I) collagen promoter. The observation that this protein localizes mostly in the cytoplasm suggests that it may be involved in a cytoplasmic function such as controlling RNA metabolism, rather than transcription. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]

RBMS3 links:

RBMS3 (HGNC:):

RBMS3 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=0.36514837).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBMS3	NM_001003793.3 linkuse as main transcript	c.648G>T	p.Glu216Asp	missense_variant	7/15	ENST00000383767.7	NP_001003793.1	Q6XE24-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBMS3	ENST00000383767.7 linkuse as main transcript	c.648G>T	p.Glu216Asp	missense_variant	7/15	1	NM_001003793.3	ENSP00000373277.2		Q6XE24-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1445508

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717006

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 20, 2024

The c.648G>T (p.E216D) alteration is located in exon 7 (coding exon 7) of the RBMS3 gene. This alteration results from a G to T substitution at nucleotide position 648, causing the glutamic acid (E) at amino acid position 216 to be replaced by an aspartic acid (D). 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

0.19

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.066

.;T;.;.;.;.;.

Eigen

Benign

-0.14

Eigen_PC

Benign

0.032

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.80

T;T;T;T;T;T;T

M_CAP

Benign

0.053

MetaRNN

Benign

0.37

T;T;T;T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.92

.;L;.;L;.;L;L

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.9

N;N;N;N;N;N;N

REVEL

Benign

0.25

Sift

Benign

0.29

T;T;T;T;T;T;T

Sift4G

Benign

0.33

T;T;T;T;T;T;T

Polyphen

0.0

.;B;.;.;B;.;B

Vest4

0.71

MutPred

0.33

.;Gain of ubiquitination at K221 (P = 0.0972);Gain of ubiquitination at K221 (P = 0.0972);Gain of ubiquitination at K221 (P = 0.0972);.;Gain of ubiquitination at K221 (P = 0.0972);Gain of ubiquitination at K221 (P = 0.0972);

MVP

0.68

MPC

0.85

ClinPred

0.74

GERP RS

4.1

Varity_R

0.22

gMVP

0.42

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over