Variant 3-29762904-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001003793.3(RBMS3):c.558-6T>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00919 in 1,593,406 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0095 ( 75 hom. )

Consequence

RBMS3
NM_001003793.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.007632

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.16

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 3-29762904-T-A is Benign according to our data. Variant chr3-29762904-T-A is described in ClinVar as [Benign]. Clinvar id is 770884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBMS3	NM_001003793.3 linkuse as main transcript	c.558-6T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000383767.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBMS3	ENST00000383767.7 linkuse as main transcript	c.558-6T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001003793.3		Q6XE24-1

Frequencies

GnomAD3 genomes

AF:

0.00637

AC:

969

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00426

Gnomad ASJ

AF:

0.00577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0107

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00766

AC:

1859

AN:

242746

Hom.:

AF XY:

0.00750

AC XY:

987

AN XY:

131574

show subpopulations

Gnomad AFR exome

AF:

0.00141

Gnomad AMR exome

AF:

0.00316

Gnomad ASJ exome

AF:

0.00436

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000934

Gnomad FIN exome

AF:

0.0137

Gnomad NFE exome

AF:

0.0119

Gnomad OTH exome

AF:

0.00867

GnomAD4 exome

AF:

0.00948

AC:

13670

AN:

1441224

Hom.:

Cov.:

AF XY:

0.00919

AC XY:

6598

AN XY:

717938

show subpopulations

Gnomad4 AFR exome

AF:

0.00138

Gnomad4 AMR exome

AF:

0.00317

Gnomad4 ASJ exome

AF:

0.00452

Gnomad4 EAS exome

AF:

0.0000508

Gnomad4 SAS exome

AF:

0.00122

Gnomad4 FIN exome

AF:

0.0131

Gnomad4 NFE exome

AF:

0.0110

Gnomad4 OTH exome

AF:

0.00844

GnomAD4 genome

AF:

0.00637

AC:

969

AN:

152182

Hom.:

Cov.:

AF XY:

0.00608

AC XY:

452

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.00161

Gnomad4 AMR

AF:

0.00426

Gnomad4 ASJ

AF:

0.00577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0107

Gnomad4 NFE

AF:

0.0101

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00855

Hom.:

Bravo

AF:

0.00578

EpiCase

AF:

0.00990

EpiControl

AF:

0.0114

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.4

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0076

dbscSNV1_RF

Benign

0.13

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