10-6112345-C-T

Variant names:

• chr10-6112345-C-T
• rs12242912
• NM_032905.5:c.840C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032905.5(RBM17):​c.840C>T​(p.Gly280Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00407 in 1,613,726 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (96 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (103 hom.)
• Consequence: RBM17 NM_032905.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.86
• Publications: 2 publications found

Genes affected

RBM17 (HGNC:16944): (RNA binding motif protein 17) This gene encodes an RNA binding protein. The encoded protein is part of the spliceosome complex and functions in the second catalytic step of mRNA splicing. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 9 and 15. [provided by RefSeq, Mar 2009]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.007).
• BP6: Variant 10-6112345-C-T is Benign according to our data. Variant chr10-6112345-C-T is described in ClinVar as Benign. ClinVar VariationId is 719467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.86 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0713 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032905.5. 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
	RBM17	NM_032905.5	MANE Select	c.840C>T	p.Gly280Gly	synonymous	Exon 8 of 12	NP_116294.1	Q96I25
	RBM17	NM_001145547.2		c.840C>T	p.Gly280Gly	synonymous	Exon 8 of 12	NP_001139019.1	Q5W009

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM17	ENST00000379888.9	TSL:1 MANE Select	c.840C>T	p.Gly280Gly	synonymous	Exon 8 of 12	ENSP00000369218.4	Q96I25
	RBM17	ENST00000446108.5	TSL:1	c.840C>T	p.Gly280Gly	synonymous	Exon 8 of 12	ENSP00000388638.1	Q96I25
	RBM17	ENST00000910323.1		c.936C>T	p.Gly312Gly	synonymous	Exon 9 of 13	ENSP00000580382.1

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 3249 AN: 151898 Hom.: 96 Cov.: 32

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00859

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.0125

GnomAD2 exomes AF: 0.00582 AC: 1458 AN: 250538 AF XY: 0.00424

Gnomad AFR exome AF: 0.0766

Gnomad AMR exome AF: 0.00414

Gnomad ASJ exome AF: 0.000995

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000309

Gnomad OTH exome AF: 0.00376

GnomAD4 exome AF: 0.00227 AC: 3325 AN: 1461710 Hom.: 103 Cov.: 31 AF XY: 0.00192 AC XY: 1399 AN XY: 727142

African (AFR) AF: 0.0750 AC: 2512 AN: 33478

American (AMR) AF: 0.00474 AC: 212 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.000765 AC: 20 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53296

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5768

European-Non Finnish (NFE) AF: 0.000230 AC: 256 AN: 1111984

Other (OTH) AF: 0.00474 AC: 286 AN: 60394

GnomAD4 genome AF: 0.0214 AC: 3250 AN: 152016 Hom.: 96 Cov.: 32 AF XY: 0.0204 AC XY: 1516 AN XY: 74290

African (AFR) AF: 0.0735 AC: 3046 AN: 41438

American (AMR) AF: 0.00852 AC: 130 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5158

South Asian (SAS) AF: 0.000417 AC: 2 AN: 4794

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10598

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 67980

Other (OTH) AF: 0.0123 AC: 26 AN: 2108

Alfa AF: 0.00871 Hom.: 61

Bravo AF: 0.0235

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.96
DANN	Benign	0.70
PhyloP100		-2.9
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.7
Mutation Taster		=98/2	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: rs12242912; hg19: chr10-6154308;