dbSNP rs367790106: RBM10:c.201+12G>A (chrX-47169510-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005676.5(RBM10):c.201+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000238 in 1,197,799 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 92 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 0.00016 ( 0 hom., 5 hem., cov: 24)

Exomes 𝑓: 0.00025 ( 0 hom. 87 hem. )

Consequence

RBM10
NM_005676.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.02

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

TARP syndrome
Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

RBM10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant X-47169510-G-A is Benign according to our data. Variant chrX-47169510-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 5 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005676.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RBM10	NM_005676.5	MANE Select	c.201+12G>A	intron	N/A	NP_005667.2
RBM10	NM_001204468.2		c.396+12G>A	intron	N/A	NP_001191397.1	P98175-5
RBM10	NM_001440861.1		c.396+12G>A	intron	N/A	NP_001427790.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RBM10	ENST00000377604.8	TSL:1 MANE Select	c.201+12G>A	intron	N/A	ENSP00000366829.3	P98175-1
RBM10	ENST00000329236.8	TSL:1	c.396+12G>A	intron	N/A	ENSP00000328848.8	P98175-5
RBM10	ENST00000628161.2	TSL:1	c.201+12G>A	intron	N/A	ENSP00000486115.1	P98175-4

Frequencies

GnomAD3 genomes

AF:

0.000159

AC:

AN:

113002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000321

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:

0.000319

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000229

AC:

AN:

157135

AF XY:

0.000144

show subpopulations

Gnomad AFR exome

AF:

0.000176

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000501

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000246

AC:

267

AN:

1084797

Hom.:

Cov.:

AF XY:

0.000246

AC XY:

AN XY:

352955

show subpopulations

African (AFR)

AF:

0.0000382

AC:

AN:

26174

American (AMR)

AF:

0.00

AC:

AN:

33516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19157

East Asian (EAS)

AF:

0.00

AC:

AN:

29720

South Asian (SAS)

AF:

0.00

AC:

AN:

52521

European-Finnish (FIN)

AF:

0.0000255

AC:

AN:

39192

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3295

European-Non Finnish (NFE)

AF:

0.000311

AC:

260

AN:

835636

Other (OTH)

AF:

0.000110

AC:

AN:

45586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000159

AC:

AN:

113002

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

AN XY:

35130

show subpopulations

African (AFR)

AF:

0.0000321

AC:

AN:

31170

American (AMR)

AF:

0.00

AC:

AN:

10815

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3553

South Asian (SAS)

AF:

0.00

AC:

AN:

2760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.000319

AC:

AN:

53288

Other (OTH)

AF:

0.00

AC:

AN:

1533

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000144

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.9

(source)

DANN

Benign

0.66

PhyloP100

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over