chr3-50077082-C-T

Position:

• chr3-50077082-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005777.3(RBM6):​c.3321C>T​(p.Tyr1107=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,611,704 control chromosomes in the GnomAD database, including 306,831 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 0.65 (33039 hom., cov: 30)
  • Exomes 𝑓: 0.61 (273792 hom.)
• Consequence: RBM6 NM_005777.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545

Genes affected

RBM6 (HGNC:9903): (RNA binding motif protein 6) Enables RNA binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.545 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM6	NM_005777.3	c.3321C>T	p.Tyr1107=	synonymous_variant	21/21	ENST00000266022.9	NP_005768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM6	ENST00000266022.9	c.3321C>T	p.Tyr1107=	synonymous_variant	21/21	1	NM_005777.3	ENSP00000266022	P1

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99104 AN: 151662 Hom.: 32993 Cov.: 30

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.639

GnomAD3 exomes AF: 0.675 AC: 169156 AN: 250726 Hom.: 58765 AF XY: 0.673 AC XY: 91220 AN XY: 135552

Gnomad AFR exome AF: 0.727

Gnomad AMR exome AF: 0.761

Gnomad ASJ exome AF: 0.735

Gnomad EAS exome AF: 0.884

Gnomad SAS exome AF: 0.826

Gnomad FIN exome AF: 0.621

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.636

GnomAD4 exome AF: 0.606 AC: 884349 AN: 1459924 Hom.: 273792 Cov.: 41 AF XY: 0.611 AC XY: 443420 AN XY: 726240

Gnomad4 AFR exome AF: 0.734

Gnomad4 AMR exome AF: 0.752

Gnomad4 ASJ exome AF: 0.733

Gnomad4 EAS exome AF: 0.870

Gnomad4 SAS exome AF: 0.822

Gnomad4 FIN exome AF: 0.617

Gnomad4 NFE exome AF: 0.565

Gnomad4 OTH exome AF: 0.624

GnomAD4 genome AF: 0.654 AC: 99204 AN: 151780 Hom.: 33039 Cov.: 30 AF XY: 0.662 AC XY: 49079 AN XY: 74166

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.678

Gnomad4 ASJ AF: 0.740

Gnomad4 EAS AF: 0.885

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.636

Alfa AF: 0.613 Hom.: 32315

Bravo AF: 0.655

Asia WGS AF: 0.798 AC: 2777 AN: 3478

EpiCase AF: 0.580

EpiControl AF: 0.578

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	2.6
DANN	Benign	0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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: rs7061; hg19: chr3-50114515; COSMIC: COSV56481132;