3-29409491-T-G

Position:

• chr3-29409491-T-G

Variant summary

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

The ENST00000383767.7(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 ENST00000383767.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
RBMS3	NM_001003793.3	c.76-25252T>G		intron_variant		ENST00000383767.7	NP_001003793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBMS3	ENST00000383767.7	c.76-25252T>G		intron_variant		1	NM_001003793.3	ENSP00000373277

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

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.487

Alfa AF: 0.401 Hom.: 16651

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

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: rs7622604; hg19: chr3-29450982;