Variant chr3-29587153-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001003793.3(RBMS3):c.347A>C(p.Gln116Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Consequence

RBMS3
NM_001003793.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88

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:

ENSG00000283563 (HGNC:):

ENSG00000283563 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBMS3	NM_001003793.3 linkuse as main transcript	c.347A>C	p.Gln116Pro	missense_variant	4/15	ENST00000383767.7	NP_001003793.1	Q6XE24-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RBMS3	ENST00000383767.7 linkuse as main transcript	c.347A>C	p.Gln116Pro	missense_variant	4/15	1	NM_001003793.3	ENSP00000373277.2	Q6XE24-1
ENSG00000283563	ENST00000635992.1 linkuse as main transcript	n.*854A>C		non_coding_transcript_exon_variant	11/14	5		ENSP00000489994.1	A0A1B0GU75
ENSG00000283563	ENST00000635992.1 linkuse as main transcript	n.*854A>C		3_prime_UTR_variant	11/14	5		ENSP00000489994.1	A0A1B0GU75

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248550

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134472

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:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000624

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

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 16, 2024

The c.347A>C (p.Q116P) alteration is located in exon 4 (coding exon 4) of the RBMS3 gene. This alteration results from a A to C substitution at nucleotide position 347, causing the glutamine (Q) at amino acid position 116 to be replaced by a proline (P). 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

Pathogenic

1.0

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

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

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

D;D;D;D;D;D;D

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.71

D;D;D;D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

.;M;.;M;.;M;M

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-4.2

D;D;D;D;D;D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0060

D;D;D;D;D;D;D

Sift4G

Uncertain

0.057

T;T;T;T;D;T;T

Polyphen

0.99, 0.98, 0.77

.;D;.;.;D;.;P

Vest4

0.64

MutPred

0.71

.;Gain of glycosylation at Q116 (P = 0.0312);Gain of glycosylation at Q116 (P = 0.0312);Gain of glycosylation at Q116 (P = 0.0312);.;Gain of glycosylation at Q116 (P = 0.0312);Gain of glycosylation at Q116 (P = 0.0312);

MVP

0.46

MPC

1.2

ClinPred

0.98

GERP RS

5.8

Varity_R

0.83

gMVP

0.79

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