Variant X-47147429-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The ENST00000329236.8(RBM10):c.143G>A(p.Arg48Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000406 in 1,208,298 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000036 ( 0 hom. 15 hem. )

Consequence

RBM10
ENST00000329236.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

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 Benign. Variant got -7 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=0.06723988).

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM10	NM_005676.5 linkuse as main transcript	c.-53G>A		5_prime_UTR_variant	2/24	ENST00000377604.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM10	ENST00000329236.8 linkuse as main transcript	c.143G>A	p.Arg48Gln	missense_variant	2/24	1		P3	P98175-5
RBM10	ENST00000377604.8 linkuse as main transcript	c.-53G>A		5_prime_UTR_variant	2/24	1	NM_005676.5	A1	P98175-1
RBM10	ENST00000628161.2 linkuse as main transcript	c.-53G>A		5_prime_UTR_variant	2/23	1			P98175-4
RBM10	ENST00000345781.10 linkuse as main transcript	c.-53G>A		5_prime_UTR_variant	2/23	2			P98175-3

Frequencies

GnomAD3 genomes

AF:

0.0000894

AC:

AN:

111872

Hom.:

Cov.:

AF XY:

0.0000588

AC XY:

AN XY:

34042

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:

0.000370

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000151

Gnomad OTH

AF:

0.000663

GnomAD3 exomes

AF:

0.0000221

AC:

AN:

180606

Hom.:

AF XY:

0.0000455

AC XY:

AN XY:

65942

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:

0.0000373

Gnomad OTH exome

AF:

0.000226

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1096372

Hom.:

Cov.:

AF XY:

0.0000414

AC XY:

AN XY:

361914

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000555

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.0000653

GnomAD4 genome

AF:

0.0000893

AC:

AN:

111926

Hom.:

Cov.:

AF XY:

0.0000586

AC XY:

AN XY:

34106

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:

0.000371

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000151

Gnomad4 OTH

AF:

0.000655

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000330

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

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

Nov 03, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.93

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.85

MetaRNN

Benign

0.067

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.50

Sift4G

Benign

0.17

Vest4

0.056

MVP

0.48

GERP RS

4.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.1

gMVP

0.12

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