rs984460

Variant names:

• chr3-29242542-A-G
• rs984460
• ENST00000635992.1:n.*582+59413A>G

Variant summary

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

The ENST00000635992.1(ENSG00000283563):​n.*582+59413A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 152,234 control chromosomes in the GnomAD database, including 325 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 0.060 (325 hom., cov: 33)
• Consequence: ENSG00000283563 ENST00000635992.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 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.*582+59413A>G		intron_variant	Intron 8 of 13	5		ENSP00000489994.1

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9056 AN: 152116 Hom.: 324 Cov.: 33

Gnomad AFR AF: 0.0450

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0459

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.0306

Gnomad FIN AF: 0.0711

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0643

Gnomad OTH AF: 0.0507

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

GnomAD4 genome AF: 0.0596 AC: 9071 AN: 152234 Hom.: 325 Cov.: 33 AF XY: 0.0598 AC XY: 4451 AN XY: 74450

Gnomad4 AFR AF: 0.0451

Gnomad4 AMR AF: 0.0459

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.0311

Gnomad4 FIN AF: 0.0711

Gnomad4 NFE AF: 0.0643

Gnomad4 OTH AF: 0.0530

Alfa AF: 0.0591 Hom.: 378

Bravo AF: 0.0580

Asia WGS AF: 0.0830 AC: 288 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.3
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: rs984460; hg19: chr3-29284033;