rs545735

Variant names:

• chr3-29077283-T-C
• rs545735
• ENST00000635992.1:n.*409-105673T>C

Variant summary

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

The ENST00000635992.1(ENSG00000283563):​n.*409-105673T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,110 control chromosomes in the GnomAD database, including 4,518 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 0.22 (4518 hom., cov: 32)
• Consequence: ENSG00000283563 ENST00000635992.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 1 publications found

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]

RBMS3-AS3 (HGNC:39989): (RBMS3 antisense RNA 3)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283563	ENST00000635992.1	n.*409-105673T>C		intron_variant	Intron 7 of 13	5		ENSP00000489994.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33654 AN: 151992 Hom.: 4514 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.222 AC: 33693 AN: 152110 Hom.: 4518 Cov.: 32 AF XY: 0.225 AC XY: 16763 AN XY: 74376

African (AFR) AF: 0.370 AC: 15349 AN: 41470

American (AMR) AF: 0.267 AC: 4082 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 498 AN: 3468

East Asian (EAS) AF: 0.159 AC: 824 AN: 5172

South Asian (SAS) AF: 0.252 AC: 1218 AN: 4824

European-Finnish (FIN) AF: 0.175 AC: 1857 AN: 10612

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9285 AN: 67972

Other (OTH) AF: 0.202 AC: 427 AN: 2116

Alfa AF: 0.193 Hom.: 612

Bravo AF: 0.231

Asia WGS AF: 0.191 AC: 665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.9
DANN	Benign	0.76
PhyloP100		1.0

Splicing

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

Other links and lift over

dbSNP: rs545735; hg19: chr3-29118774;