NM_001003793.3:c.637+48923G>A

Variant names:

• chr3-29811912-G-A
• rs10510628
• NM_001003793.3:c.637+48923G>A

Variant summary

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

The NM_001003793.3(RBMS3):​c.637+48923G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,010 control chromosomes in the GnomAD database, including 8,699 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 0.33 (8699 hom., cov: 32)
• Consequence: RBMS3 NM_001003793.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 13 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.389 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.637+48923G>A		intron	N/A	NP_001003793.1
	RBMS3	NM_001330696.1		c.634+48923G>A		intron	N/A	NP_001317625.1
	RBMS3	NM_001177712.2		c.637+48923G>A		intron	N/A	NP_001171183.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBMS3	ENST00000383767.7	TSL:1 MANE Select	c.637+48923G>A		intron	N/A	ENSP00000373277.2
	RBMS3	ENST00000456853.1	TSL:1	c.637+48923G>A		intron	N/A	ENSP00000400519.1
	RBMS3	ENST00000273139.13	TSL:1	c.637+48923G>A		intron	N/A	ENSP00000273139.9

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50051 AN: 151892 Hom.: 8697 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.0686

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.329 AC: 50087 AN: 152010 Hom.: 8699 Cov.: 32 AF XY: 0.321 AC XY: 23828 AN XY: 74298

African (AFR) AF: 0.273 AC: 11343 AN: 41478

American (AMR) AF: 0.310 AC: 4722 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1198 AN: 3470

East Asian (EAS) AF: 0.0688 AC: 356 AN: 5178

South Asian (SAS) AF: 0.166 AC: 798 AN: 4816

European-Finnish (FIN) AF: 0.362 AC: 3815 AN: 10546

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26670 AN: 67954

Other (OTH) AF: 0.337 AC: 711 AN: 2110

Alfa AF: 0.367 Hom.: 45436

Bravo AF: 0.329

Asia WGS AF: 0.155 AC: 545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.70
PhyloP100		0.30
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: rs10510628; hg19: chr3-29853403;