3-28919494-G-T

Position:

• chr3-28919494-G-T

Variant summary

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

The ENST00000636680.2(RBMS3):​c.282+54202G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0298 in 152,084 control chromosomes in the GnomAD database, including 210 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 0.030 (210 hom., cov: 32)
• Consequence: RBMS3 ENST00000636680.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBMS3	ENST00000636680.2	c.282+54202G>T		intron_variant		5
RBMS3	ENST00000637842.1	c.148+20932G>T		intron_variant, NMD_transcript_variant		5
RBMS3	ENST00000636582.1	n.238+54202G>T		intron_variant, non_coding_transcript_variant		5
RBMS3	ENST00000636900.1	n.238+54202G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0298 AC: 4523 AN: 151968 Hom.: 208 Cov.: 32

Gnomad AFR AF: 0.0241

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0358

Gnomad EAS AF: 0.0874

Gnomad SAS AF: 0.0371

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00999

Gnomad OTH AF: 0.0325

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

GnomAD4 genome AF: 0.0298 AC: 4531 AN: 152084 Hom.: 210 Cov.: 32 AF XY: 0.0327 AC XY: 2433 AN XY: 74348

Gnomad4 AFR AF: 0.0240

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.0358

Gnomad4 EAS AF: 0.0872

Gnomad4 SAS AF: 0.0375

Gnomad4 FIN AF: 0.0101

Gnomad4 NFE AF: 0.00999

Gnomad4 OTH AF: 0.0365

Alfa AF: 0.0178 Hom.: 16

Bravo AF: 0.0373

Asia WGS AF: 0.0920 AC: 317 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.19

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs952629; hg19: chr3-28960985;