rs2023953

Variant names:

• chr3-50066484-G-A
• rs2023953
• NM_005777.3:c.2925G>A
• RBM6 p.Gln975Gln

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_005777.3(RBM6):​c.2925G>A​(p.Gln975Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,613,370 control chromosomes in the GnomAD database, including 8,518 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 0.094 (744 hom., cov: 32)
  • Exomes 𝑓: 0.10 (7774 hom.)
• Consequence: RBM6 NM_005777.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• Publications: 21 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=1.85 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.101 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.2925G>A	p.Gln975Gln	synonymous	Exon 17 of 21	NP_005768.1	P78332-1
	RBM6	NM_001349194.2		c.1383G>A	p.Gln461Gln	synonymous	Exon 14 of 18	NP_001336123.1
	RBM6	NM_001167582.2		c.1359G>A	p.Gln453Gln	synonymous	Exon 13 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.2925G>A	p.Gln975Gln	synonymous	Exon 17 of 21	ENSP00000266022.4	P78332-1
	RBM6	ENST00000442092.5	TSL:1	c.1359G>A	p.Gln453Gln	synonymous	Exon 13 of 17	ENSP00000393530.1	P78332-2
	RBM6	ENST00000858028.1		c.2925G>A	p.Gln975Gln	synonymous	Exon 17 of 21	ENSP00000528087.1

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14266 AN: 152166 Hom.: 741 Cov.: 32

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0510

Gnomad SAS AF: 0.0569

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0946

GnomAD2 exomes AF: 0.0974 AC: 24022 AN: 246580 AF XY: 0.0941

Gnomad AFR exome AF: 0.0751

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.0505

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.101

GnomAD4 exome AF: 0.101 AC: 148052 AN: 1461086 Hom.: 7774 Cov.: 32 AF XY: 0.0994 AC XY: 72235 AN XY: 726812

African (AFR) AF: 0.0744 AC: 2491 AN: 33472

American (AMR) AF: 0.127 AC: 5698 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 3909 AN: 26136

East Asian (EAS) AF: 0.0589 AC: 2338 AN: 39700

South Asian (SAS) AF: 0.0530 AC: 4569 AN: 86256

European-Finnish (FIN) AF: 0.0989 AC: 5217 AN: 52754

Middle Eastern (MID) AF: 0.0756 AC: 436 AN: 5768

European-Non Finnish (NFE) AF: 0.106 AC: 117534 AN: 1111896

Other (OTH) AF: 0.0971 AC: 5860 AN: 60380

GnomAD4 genome AF: 0.0938 AC: 14284 AN: 152284 Hom.: 744 Cov.: 32 AF XY: 0.0930 AC XY: 6921 AN XY: 74454

African (AFR) AF: 0.0768 AC: 3193 AN: 41556

American (AMR) AF: 0.104 AC: 1594 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 545 AN: 3470

East Asian (EAS) AF: 0.0511 AC: 265 AN: 5184

South Asian (SAS) AF: 0.0572 AC: 276 AN: 4828

European-Finnish (FIN) AF: 0.103 AC: 1087 AN: 10604

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7021 AN: 68030

Other (OTH) AF: 0.0936 AC: 198 AN: 2116

Alfa AF: 0.102 Hom.: 1703

Bravo AF: 0.0950

Asia WGS AF: 0.0640 AC: 223 AN: 3478

EpiCase AF: 0.109

EpiControl AF: 0.110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	5.6
DANN	Benign	0.68
PhyloP100		1.9
PromoterAI		-0.0072	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=251/49	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2023953;

hg19: chr3-50103917;

COSMIC: COSV56487889;

COSMIC: COSV56487889;