X-47169433-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4

The NM_005676.5(RBM10):c.136C>T(p.Arg46Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000146 in 1,097,737 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R46H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.000015 ( 0 hom. 5 hem. )

Consequence

RBM10
NM_005676.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.87

Variant links:

Genes affected

RBM10 (HGNC:9896): (RNA binding motif protein 10) This gene encodes a nuclear protein that belongs to a family proteins that contain an RNA-binding motif. The encoded protein associates with hnRNP proteins and may be involved in regulating alternative splicing. Defects in this gene are the cause of the X-linked recessive disorder, TARP syndrome. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2011]

RBM10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP2

Missense variant where missense usually causes diseases, RBM10

BP4

Computational evidence support a benign effect (MetaRNN=0.2754314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM10	NM_005676.5 linkuse as main transcript	c.136C>T	p.Arg46Cys	missense_variant	3/24	ENST00000377604.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM10	ENST00000377604.8 linkuse as main transcript	c.136C>T	p.Arg46Cys	missense_variant	3/24	1	NM_005676.5	A1	P98175-1
RBM10	ENST00000329236.8 linkuse as main transcript	c.331C>T	p.Arg111Cys	missense_variant	3/24	1		P3	P98175-5
RBM10	ENST00000628161.2 linkuse as main transcript	c.136C>T	p.Arg46Cys	missense_variant	3/23	1			P98175-4
RBM10	ENST00000345781.10 linkuse as main transcript	c.136C>T	p.Arg46Cys	missense_variant	3/23	2			P98175-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000165

AC:

AN:

181998

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

66558

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000106

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000146

AC:

AN:

1097737

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

363103

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000154

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Nov 15, 2022

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 46 of the RBM10 protein (p.Arg46Cys). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with RBM10-related conditions. This variant is present in population databases (rs781848934, gnomAD 0.01%), including at least one homozygous and/or hemizygous individual. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.36

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Uncertain

0.51

D;.;.;.

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.28

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.0

M;M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.5

D;.;D;.

REVEL

Benign

0.18

Sift

Pathogenic

0.0

D;.;T;.

Sift4G

Uncertain

0.023

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.28

MutPred

0.33

Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);.;

MVP

0.66

MPC

3.1

ClinPred

0.77

GERP RS

4.7

Varity_R

0.45

gMVP

0.59

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