chrX-115189625-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_001145346.2(RBMXL3):c.184G>A(p.Ala62Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,167,961 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 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 0.000018 ( 0 hom., 1 hem., cov: 25)

Exomes 𝑓: 0.000013 ( 0 hom. 7 hem. )

Consequence

RBMXL3
NM_001145346.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.67

Publications

0 publications found

Variant links:

Genes affected

RBMXL3 (HGNC:26859): (RBMX like 3) Predicted to enable mRNA binding activity and snRNA binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Predicted to be part of U12-type spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

RBMXL3 links:

LRCH2 (HGNC:29292): (leucine rich repeats and calponin homology domain containing 2) This gene encodes a member of the leucine-rich repeat and calponin homology domain-containing protein family. These family members contain multiple N-terminal leucine-rich repeats, in addition to a C-terminal calponin homology domain, a type of domain that mediates interactions with actin filaments. These proteins are conserved across animal species, and studies of a similar Drosophila protein indicate a function as a cytoskeletal scaffolding protein. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2011]

LRCH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.4224872).

BS2

High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBMXL3	NM_001145346.2 link	c.184G>A	p.Ala62Thr	missense_variant	Exon 1 of 1	ENST00000424776.5	NP_001138818.1	Q8N7X1
LRCH2	NM_020871.4 link	c.350-1255C>T		intron_variant	Intron 1 of 20	ENST00000317135.13	NP_065922.3	Q5VUJ6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RBMXL3	ENST00000424776.5 link	c.184G>A	p.Ala62Thr	missense_variant	Exon 1 of 1	6	NM_001145346.2	ENSP00000417451.3	Q8N7X1
LRCH2	ENST00000317135.13 link	c.350-1255C>T		intron_variant	Intron 1 of 20	1	NM_020871.4	ENSP00000325091.8	Q5VUJ6-1
LRCH2	ENST00000538422.2 link	c.350-1255C>T		intron_variant	Intron 1 of 19	1		ENSP00000439366.1	Q5VUJ6-2

Frequencies

GnomAD3 genomes

AF:

0.0000177

AC:

AN:

113234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000640

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:

0.00

GnomAD2 exomes

AF:

0.0000169

AC:

AN:

117999

AF XY:

0.0000480

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000437

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000133

AC:

AN:

1054727

Hom.:

Cov.:

AF XY:

0.0000203

AC XY:

AN XY:

345085

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24935

American (AMR)

AF:

0.00

AC:

AN:

27952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18647

East Asian (EAS)

AF:

0.00

AC:

AN:

27168

South Asian (SAS)

AF:

0.0000401

AC:

AN:

49891

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37681

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4091

European-Non Finnish (NFE)

AF:

0.0000122

AC:

AN:

819906

Other (OTH)

AF:

0.0000450

AC:

AN:

44456

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:

0.0000177

AC:

AN:

113234

Hom.:

Cov.:

AF XY:

0.0000283

AC XY:

AN XY:

35370

show subpopulations

African (AFR)

AF:

0.0000640

AC:

AN:

31230

American (AMR)

AF:

0.00

AC:

AN:

10830

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2663

East Asian (EAS)

AF:

0.00

AC:

AN:

3578

South Asian (SAS)

AF:

0.00

AC:

AN:

2764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6319

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53400

Other (OTH)

AF:

0.00

AC:

AN:

1525

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000418

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 31, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.184G>A (p.A62T) alteration is located in exon 1 (coding exon 1) of the RBMXL3 gene. This alteration results from a G to A substitution at nucleotide position 184, causing the alanine (A) at amino acid position 62 to be replaced by a threonine (T). 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

Pathogenic

0.80

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Benign

-0.090

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0049

MetaRNN

Benign

0.42

MetaSVM

Uncertain

0.37

MutationAssessor

Uncertain

2.7

PhyloP100

4.7

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.43

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.037

Polyphen

1.0

Vest4

0.39

MVP

0.12

ClinPred

0.80

GERP RS

0.56

PromoterAI

-0.030

Neutral

(source)

Varity_R

0.35

gMVP

0.80

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over