Genetic Variant RBMX:c.389-17T>C (chrX-136876672-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002139.4(RBMX):c.389-17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,150,884 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 (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 2 hem., cov: 21)

Exomes 𝑓: 0.0000096 ( 0 hom. 3 hem. )

Consequence

RBMX
NM_002139.4 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04

Publications

0 publications found

Variant links:

Genes affected

RBMX (HGNC:9910): (RNA binding motif protein X-linked) This gene belongs to the RBMY gene family which includes candidate Y chromosome spermatogenesis genes. This gene, an active X chromosome homolog of the Y chromosome RBMY gene, is widely expressed whereas the RBMY gene evolved a male-specific function in spermatogenesis. Pseudogenes of this gene, found on chromosomes 1, 4, 9, 11, and 6, were likely derived by retrotransposition from the original gene. Alternatively spliced transcript variants encoding different isoforms have been identified. A snoRNA gene (SNORD61) is found in one of its introns. [provided by RefSeq, Sep 2009]

RBMX Gene-Disease associations (from GenCC):

syndromic X-linked intellectual disability Shashi type
Inheritance: Unknown, XL Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

RBMX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BS2

High Hemizygotes in GnomAd4 at 2 Unknown,XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002139.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RBMX	NM_002139.4	MANE Select	c.389-17T>C	intron	N/A	NP_002130.2	P38159-1
RBMX	NM_001164803.2		c.217-1087T>C	intron	N/A	NP_001158275.1	P38159-3
RBMX	NR_028476.2		n.372-17T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RBMX	ENST00000320676.11	TSL:1 MANE Select	c.389-17T>C	intron	N/A	ENSP00000359645.3	P38159-1
RBMX	ENST00000562646.5	TSL:1	c.389-17T>C	intron	N/A	ENSP00000457051.1	H3BT71
RBMX	ENST00000568578.5	TSL:1	n.217-17T>C	intron	N/A	ENSP00000457691.1	H3BR27

Frequencies

GnomAD3 genomes

AF:

0.0000455

AC:

AN:

109952

Hom.:

Cov.:

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:

0.0000949

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

141567

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000961

AC:

AN:

1040932

Hom.:

Cov.:

AF XY:

0.00000916

AC XY:

AN XY:

327358

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23640

American (AMR)

AF:

0.00

AC:

AN:

24130

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16755

East Asian (EAS)

AF:

0.00

AC:

AN:

29402

South Asian (SAS)

AF:

0.00

AC:

AN:

47433

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38856

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3885

European-Non Finnish (NFE)

AF:

0.0000111

AC:

AN:

813273

Other (OTH)

AF:

0.0000230

AC:

AN:

43558

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000455

AC:

AN:

109952

Hom.:

Cov.:

AF XY:

0.0000621

AC XY:

AN XY:

32200

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30160

American (AMR)

AF:

0.00

AC:

AN:

10264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2637

East Asian (EAS)

AF:

0.00

AC:

AN:

3480

South Asian (SAS)

AF:

0.00

AC:

AN:

2565

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5768

Middle Eastern (MID)

AF:

0.00

AC:

AN:

235

European-Non Finnish (NFE)

AF:

0.0000949

AC:

AN:

52702

Other (OTH)

AF:

0.00

AC:

AN:

1461

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

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:

0.000214

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.8

(source)

DANN

Benign

0.80

PhyloP100

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

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