X-48575111-C-G

Variant summary

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

The NM_006743.5(RBM3):c.-13-57C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 110,678 control chromosomes in the GnomAD database, including 9,715 homozygotes. There are 15,848 hemizygotes in GnomAD. 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 0.47 (9715 hom., 15848 hem., cov: 23)
  • Exomes 𝑓: 0.57 (90624 hom. 125167 hem.)
  • Failed GnomAD Quality Control
• Consequence: RBM3 NM_006743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

Genes affected

RBM3 (HGNC:9900): (RNA binding motif protein 3) This gene is a member of the glycine-rich RNA-binding protein family and encodes a protein with one RNA recognition motif (RRM) domain. Expression of this gene is induced by cold shock and low oxygen tension. A pseudogene exists on chromosome 1. Multiple alternatively spliced transcript variants that are predicted to encode different isoforms have been characterized although some of these variants fit nonsense-mediated decay (NMD) criteria. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM3	NM_006743.5	c.-13-57C>G		intron_variant		ENST00000376759.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM3	ENST00000376759.8	c.-13-57C>G		intron_variant		1	NM_006743.5	P1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 52555 AN: 110627 Hom.: 9731 Cov.: 23 AF XY: 0.482 AC XY: 15829 AN XY: 32865

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.494

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.572 AC: 439090 AN: 767708 Hom.: 90624 Cov.: 12 AF XY: 0.584 AC XY: 125167 AN XY: 214212

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.579

Gnomad4 ASJ exome AF: 0.689

Gnomad4 EAS exome AF: 0.472

Gnomad4 SAS exome AF: 0.571

Gnomad4 FIN exome AF: 0.580

Gnomad4 NFE exome AF: 0.585

Gnomad4 OTH exome AF: 0.563

GnomAD4 genome AF: 0.475 AC: 52542 AN: 110678 Hom.: 9715 Cov.: 23 AF XY: 0.481 AC XY: 15848 AN XY: 32926

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.495

Alfa AF: 0.508 Hom.: 3654

Bravo AF: 0.465

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.54
Dann	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2249583; hg19: chrX-48433499; COSMIC: COSV63202677; COSMIC: COSV63202677;