Variant chrX-47169422-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4BP6_Moderate

The NM_005676.5(RBM10):c.125G>A(p.Arg42His) variant causes a missense change. The variant allele was found at a frequency of 0.00000165 in 1,210,488 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

RBM10
NM_005676.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.94

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), RBM10. . Gene score misZ 4.4623 (greater than the threshold 3.09). GenCC has associacion of gene with TARP syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.29169574).

BP6

Variant X-47169422-G-A is Benign according to our data. Variant chrX-47169422-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1998888.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM10	NM_005676.5 linkuse as main transcript	c.125G>A	p.Arg42His	missense_variant	3/24	ENST00000377604.8	NP_005667.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM10	ENST00000377604.8 linkuse as main transcript	c.125G>A	p.Arg42His	missense_variant	3/24	1	NM_005676.5	ENSP00000366829	A1	P98175-1
RBM10	ENST00000329236.8 linkuse as main transcript	c.320G>A	p.Arg107His	missense_variant	3/24	1		ENSP00000328848	P3	P98175-5
RBM10	ENST00000628161.2 linkuse as main transcript	c.125G>A	p.Arg42His	missense_variant	3/23	1		ENSP00000486115		P98175-4
RBM10	ENST00000345781.10 linkuse as main transcript	c.125G>A	p.Arg42His	missense_variant	3/23	2		ENSP00000329659		P98175-3

Frequencies

GnomAD3 genomes

AF:

0.00000889

AC:

AN:

112496

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

34666

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:

0.000282

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097992

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363352

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.00000889

AC:

AN:

112496

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

34666

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000282

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.35

T;.;.;.

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.077

MetaRNN

Benign

0.29

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M;M;.

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-2.3

N;.;N;.

REVEL

Benign

0.22

Sift

Pathogenic

0.0

D;.;D;.

Sift4G

Uncertain

0.0080

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.19

MutPred

0.37

Gain of phosphorylation at Y44 (P = 0.1297);Gain of phosphorylation at Y44 (P = 0.1297);Gain of phosphorylation at Y44 (P = 0.1297);.;

MVP

0.73

MPC

2.9

ClinPred

0.97

GERP RS

4.5

Varity_R

0.42

gMVP

0.72

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