3-29409491-T-G

Variant names:

• chr3-29409491-T-G
• rs7622604
• NM_001003793.3:c.76-25252T>G

Variant summary

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

The NM_001003793.3(RBMS3):​c.76-25252T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 152,090 control chromosomes in the GnomAD database, including 22,602 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 0.52 (22602 hom., cov: 33)
• Consequence: RBMS3 NM_001003793.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBMS3	NM_001003793.3	c.76-25252T>G		intron_variant	Intron 1 of 14	ENST00000383767.7	NP_001003793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMS3	ENST00000383767.7	c.76-25252T>G		intron_variant	Intron 1 of 14	1	NM_001003793.3	ENSP00000373277.2
ENSG00000283563	ENST00000635992.1	n.*583-25252T>G		intron_variant	Intron 8 of 13	5		ENSP00000489994.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78300 AN: 151972 Hom.: 22560 Cov.: 33

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.515 AC: 78392 AN: 152090 Hom.: 22602 Cov.: 33 AF XY: 0.518 AC XY: 38487 AN XY: 74354

African (AFR) AF: 0.780 AC: 32370 AN: 41514

American (AMR) AF: 0.459 AC: 7017 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1457 AN: 3466

East Asian (EAS) AF: 0.646 AC: 3339 AN: 5168

South Asian (SAS) AF: 0.543 AC: 2616 AN: 4818

European-Finnish (FIN) AF: 0.429 AC: 4530 AN: 10562

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25630 AN: 67978

Other (OTH) AF: 0.487 AC: 1023 AN: 2102

Alfa AF: 0.415 Hom.: 23062

Bravo AF: 0.531

Asia WGS AF: 0.620 AC: 2153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.56
PhyloP100		-0.11
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: rs7622604; hg19: chr3-29450982;