Variant 10-6101335-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_032905.5(RBM17):c.188C>T(p.Ser63Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00024 in 1,613,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

RBM17
NM_032905.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.30

Variant links:

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]

RBM17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, RBM17

BP4

Computational evidence support a benign effect (MetaRNN=0.07481283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM17	NM_032905.5 linkuse as main transcript	c.188C>T	p.Ser63Leu	missense_variant	3/12	ENST00000379888.9
RBM17	NM_001145547.2 linkuse as main transcript	c.188C>T	p.Ser63Leu	missense_variant	3/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM17	ENST00000379888.9 linkuse as main transcript	c.188C>T	p.Ser63Leu	missense_variant	3/12	1	NM_032905.5	P1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000211

AC:

AN:

251028

Hom.:

AF XY:

0.000228

AC XY:

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000449

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000254

AC:

371

AN:

1461348

Hom.:

Cov.:

AF XY:

0.000234

AC XY:

170

AN XY:

727026

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000317

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000112

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000196

Hom.:

Bravo

AF:

0.000144

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000255

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 22, 2024

The c.188C>T (p.S63L) alteration is located in exon 3 (coding exon 2) of the RBM17 gene. This alteration results from a C to T substitution at nucleotide position 188, causing the serine (S) at amino acid position 63 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;.;T;T;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.099

FATHMM_MKL

Benign

0.68

M_CAP

Benign

0.011

MetaRNN

Benign

0.075

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

L;.;.;L;.

MutationTaster

Benign

0.56

D;D

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-2.5

D;D;D;D;D

REVEL

Benign

0.031

Sift

Benign

0.13

T;T;T;T;T

Sift4G

Benign

0.28

T;T;T;T;T

Polyphen

0.0030

B;.;.;B;.

Vest4

0.26

MVP

0.33

MPC

0.81

ClinPred

0.091

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.28

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over