3-50077082-C-T

Variant names:

• chr3-50077082-C-T
• rs7061
• NM_005777.3:c.3321C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005777.3(RBM6):​c.3321C>T​(p.Tyr1107Tyr) 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
• Publications: 41 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005777.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM6	NM_005777.3	MANE Select	c.3321C>T	p.Tyr1107Tyr	synonymous	Exon 21 of 21	NP_005768.1	P78332-1
	RBM6	NM_001349194.2		c.1779C>T	p.Tyr593Tyr	synonymous	Exon 18 of 18	NP_001336123.1
	RBM6	NM_001167582.2		c.1755C>T	p.Tyr585Tyr	synonymous	Exon 17 of 17	NP_001161054.1	P78332-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM6	ENST00000266022.9	TSL:1 MANE Select	c.3321C>T	p.Tyr1107Tyr	synonymous	Exon 21 of 21	ENSP00000266022.4	P78332-1
	RBM6	ENST00000442092.5	TSL:1	c.1755C>T	p.Tyr585Tyr	synonymous	Exon 17 of 17	ENSP00000393530.1	P78332-2
	RBM6	ENST00000858028.1		c.3345C>T	p.Tyr1115Tyr	synonymous	Exon 21 of 21	ENSP00000528087.1

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

GnomAD2 exomes AF: 0.675 AC: 169156 AN: 250726 AF XY: 0.673

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 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

African (AFR) AF: 0.734 AC: 24494 AN: 33384

American (AMR) AF: 0.752 AC: 33541 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 19135 AN: 26094

East Asian (EAS) AF: 0.870 AC: 34502 AN: 39666

South Asian (SAS) AF: 0.822 AC: 70819 AN: 86136

European-Finnish (FIN) AF: 0.617 AC: 32929 AN: 53350

Middle Eastern (MID) AF: 0.648 AC: 3456 AN: 5332

European-Non Finnish (NFE) AF: 0.565 AC: 627895 AN: 1111098

Other (OTH) AF: 0.624 AC: 37578 AN: 60262

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

African (AFR) AF: 0.729 AC: 30167 AN: 41382

American (AMR) AF: 0.678 AC: 10321 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2568 AN: 3468

East Asian (EAS) AF: 0.885 AC: 4558 AN: 5150

South Asian (SAS) AF: 0.828 AC: 3991 AN: 4818

European-Finnish (FIN) AF: 0.618 AC: 6507 AN: 10522

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39056 AN: 67916

Other (OTH) AF: 0.636 AC: 1340 AN: 2106

Alfa AF: 0.613 Hom.: 36088

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	2.6
DANN	Benign	0.32
PhyloP100		0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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