Variant X-47169412-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_005676.5(RBM10):c.115A>G(p.Met39Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000033 in 1,210,525 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000036 ( 0 hom. 12 hem. )

Consequence

RBM10
NM_005676.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.88

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 Likely_benign. Variant got -5 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=0.14047113).

BS2

High Hemizygotes in GnomAdExome4 at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM10	NM_005676.5 linkuse as main transcript	c.115A>G	p.Met39Val	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.115A>G	p.Met39Val	missense_variant	3/24	1	NM_005676.5	A1	P98175-1
RBM10	ENST00000329236.8 linkuse as main transcript	c.310A>G	p.Met104Val	missense_variant	3/24	1		P3	P98175-5
RBM10	ENST00000628161.2 linkuse as main transcript	c.115A>G	p.Met39Val	missense_variant	3/23	1			P98175-4
RBM10	ENST00000345781.10 linkuse as main transcript	c.115A>G	p.Met39Val	missense_variant	3/23	2			P98175-3

Frequencies

GnomAD3 genomes

AF:

0.00000889

AC:

AN:

112465

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34623

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:

0.00

Gnomad OTH

AF:

0.000657

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

182995

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

67495

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000367

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000355

AC:

AN:

1098060

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

363418

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:

0.0000463

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000889

AC:

AN:

112465

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34623

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:

0.00

Gnomad4 OTH

AF:

0.000657

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.115A>G (p.M39V) alteration is located in exon 3 (coding exon 2) of the RBM10 gene. This alteration results from a A to G substitution at nucleotide position 115, causing the methionine (M) at amino acid position 39 to be replaced by a valine (V). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.24

T;.;.;.

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L;L;.

MutationTaster

Benign

0.94

N;N;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.6

N;.;N;.

REVEL

Benign

0.11

Sift

Benign

0.045

D;.;T;.

Sift4G

Benign

0.20

T;T;T;T

Polyphen

0.71

P;B;B;.

Vest4

0.15

MutPred

0.27

Gain of phosphorylation at Y41 (P = 0.1683);Gain of phosphorylation at Y41 (P = 0.1683);Gain of phosphorylation at Y41 (P = 0.1683);.;

MVP

0.52

MPC

2.5

ClinPred

0.32

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

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