3-28923310-C-G

Position:

• chr3-28923310-C-G

Variant summary

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

The ENST00000635992.1(ENSG00000283563):​n.*408+58018C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 152,056 control chromosomes in the GnomAD database, including 333 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 0.048 (333 hom., cov: 32)
• Consequence: ENSG00000283563 ENST00000635992.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550

Genes affected

ENSG00000283563 (HGNC:):

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.28923310C>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000283563	ENST00000635992.1	n.*408+58018C>G		intron_variant		5		ENSP00000489994.1

Frequencies

GnomAD3 genomes AF: 0.0482 AC: 7323 AN: 151938 Hom.: 332 Cov.: 32

Gnomad AFR AF: 0.0963

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0387

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.0928

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.00679

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0164

Gnomad OTH AF: 0.0459

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

GnomAD4 genome AF: 0.0483 AC: 7338 AN: 152056 Hom.: 333 Cov.: 32 AF XY: 0.0508 AC XY: 3773 AN XY: 74336

Gnomad4 AFR AF: 0.0962

Gnomad4 AMR AF: 0.0388

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.0932

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.00679

Gnomad4 NFE AF: 0.0164

Gnomad4 OTH AF: 0.0455

Alfa AF: 0.0355 Hom.: 23

Bravo AF: 0.0508

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.68
DANN	Benign	0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4016429; hg19: chr3-28964801;