3-28952016-C-T

Position:

• chr3-28952016-C-T

Variant summary

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

The ENST00000636680.2(RBMS3):​c.282+86724C>T 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 151,912 control chromosomes in the GnomAD database, including 23,100 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 0.51 (23100 hom., cov: 32)
• Consequence: RBMS3 ENST00000636680.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.828

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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBMS3	ENST00000636680.2	c.282+86724C>T		intron_variant		5		ENSP00000490271
RBMS3	ENST00000637842.1	c.148+53454C>T		intron_variant, NMD_transcript_variant		5		ENSP00000489718
RBMS3	ENST00000636582.1	n.239-23589C>T		intron_variant, non_coding_transcript_variant		5
RBMS3	ENST00000636900.1	n.238+86724C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78183 AN: 151794 Hom.: 23106 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.515 AC: 78182 AN: 151912 Hom.: 23100 Cov.: 32 AF XY: 0.522 AC XY: 38755 AN XY: 74250

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.838

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.615

Gnomad4 OTH AF: 0.528

Alfa AF: 0.597 Hom.: 35593

Bravo AF: 0.504

Asia WGS AF: 0.644 AC: 2241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.6
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6768946; hg19: chr3-28993507;