3-29422477-C-T

Variant names:

• chr3-29422477-C-T
• rs7634956
• NM_001003793.3:c.76-12266C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001003793.3(RBMS3):​c.76-12266C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 151,082 control chromosomes in the GnomAD database, including 42,367 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 0.75 (42367 hom., cov: 29)
• Consequence: RBMS3 NM_001003793.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.565
• Publications: 2 publications found

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]

ENSG00000283563 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003793.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBMS3	NM_001003793.3	MANE Select	c.76-12266C>T		intron	N/A	NP_001003793.1	Q6XE24-1
	RBMS3	NM_001330696.1		c.76-12269C>T		intron	N/A	NP_001317625.1	C9JIJ9
	RBMS3	NM_001177712.2		c.76-12266C>T		intron	N/A	NP_001171183.1	Q6XE24-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBMS3	ENST00000383767.7	TSL:1 MANE Select	c.76-12266C>T		intron	N/A	ENSP00000373277.2	Q6XE24-1
	RBMS3	ENST00000456853.1	TSL:1	c.76-12266C>T		intron	N/A	ENSP00000400519.1	Q6XE24-2
	RBMS3	ENST00000273139.13	TSL:1	c.76-12266C>T		intron	N/A	ENSP00000273139.9	Q6XE24-4

Frequencies

GnomAD3 genomes AF: 0.747 AC: 112784 AN: 150972 Hom.: 42334 Cov.: 29

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.928

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.747 AC: 112868 AN: 151082 Hom.: 42367 Cov.: 29 AF XY: 0.751 AC XY: 55386 AN XY: 73738

African (AFR) AF: 0.771 AC: 31744 AN: 41162

American (AMR) AF: 0.815 AC: 12351 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2618 AN: 3468

East Asian (EAS) AF: 0.927 AC: 4767 AN: 5140

South Asian (SAS) AF: 0.846 AC: 4074 AN: 4814

European-Finnish (FIN) AF: 0.662 AC: 6733 AN: 10172

Middle Eastern (MID) AF: 0.653 AC: 188 AN: 288

European-Non Finnish (NFE) AF: 0.709 AC: 48106 AN: 67878

Other (OTH) AF: 0.743 AC: 1554 AN: 2092

Alfa AF: 0.723 Hom.: 23377

Bravo AF: 0.757

Asia WGS AF: 0.855 AC: 2956 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.60
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7634956; hg19: chr3-29463968;