3-29533972-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001003793.3(RBMS3):c.307+45473G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 152,202 control chromosomes in the GnomAD database, including 208 homozygotes. 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: 𝑓 0.046 (208 hom., cov: 32)
• Consequence: RBMS3 NM_001003793.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

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-AS2 (HGNC:39988): (RBMS3 antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBMS3	NM_001003793.3	c.307+45473G>T		intron_variant		ENST00000383767.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBMS3	ENST00000383767.7	c.307+45473G>T		intron_variant		1	NM_001003793.3
RBMS3-AS2	ENST00000629416.2	n.381+3654C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0459 AC: 6988 AN: 152084 Hom.: 207 Cov.: 32

Gnomad AFR AF: 0.0152

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0516

Gnomad ASJ AF: 0.0540

Gnomad EAS AF: 0.0776

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0427

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0558

Gnomad OTH AF: 0.0517

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0459 AC: 6990 AN: 152202 Hom.: 208 Cov.: 32 AF XY: 0.0456 AC XY: 3391 AN XY: 74406

Gnomad4 AFR AF: 0.0152

Gnomad4 AMR AF: 0.0512

Gnomad4 ASJ AF: 0.0540

Gnomad4 EAS AF: 0.0776

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0427

Gnomad4 NFE AF: 0.0558

Gnomad4 OTH AF: 0.0568

Alfa AF: 0.0546 Hom.: 553

Bravo AF: 0.0441

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.1
Dann	Benign	0.69

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

Other links and lift over

dbSNP: rs1530057; hg19: chr3-29575463; COSMIC: COSV56140242;