X-115189739-G-A

Position:

chrX-115189739-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000317135.13(LRCH2):c.350-1369C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000054 in 1,165,615 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 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 0.000053 ( 0 hom., 1 hem., cov: 26)

Exomes 𝑓: 0.000054 ( 0 hom. 15 hem. )

Consequence

LRCH2
ENST00000317135.13 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.53

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.057591528).

BS2

High Hemizygotes in GnomAdExome4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBMXL3	NM_001145346.2 linkuse as main transcript	c.298G>A	p.Gly100Ser	missense_variant	1/1	ENST00000424776.5	NP_001138818.1
LRCH2	NM_020871.4 linkuse as main transcript	c.350-1369C>T		intron_variant		ENST00000317135.13	NP_065922.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBMXL3	ENST00000424776.5 linkuse as main transcript	c.298G>A	p.Gly100Ser	missense_variant	1/1		NM_001145346.2	ENSP00000417451	P1
LRCH2	ENST00000317135.13 linkuse as main transcript	c.350-1369C>T		intron_variant		1	NM_020871.4	ENSP00000325091	P2	Q5VUJ6-1
LRCH2	ENST00000538422.2 linkuse as main transcript	c.350-1369C>T		intron_variant		1		ENSP00000439366	A2	Q5VUJ6-2

Frequencies

GnomAD3 genomes

AF:

0.0000530

AC:

AN:

113194

Hom.:

Cov.:

AF XY:

0.0000283

AC XY:

AN XY:

35330

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000923

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:

0.0000937

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000445

AC:

AN:

112289

Hom.:

AF XY:

0.0000250

AC XY:

AN XY:

39995

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:

0.000117

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000542

AC:

AN:

1052421

Hom.:

Cov.:

AF XY:

0.0000436

AC XY:

AN XY:

343747

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:

0.0000814

Gnomad4 NFE exome

AF:

0.0000623

Gnomad4 OTH exome

AF:

0.0000677

GnomAD4 genome

AF:

0.0000530

AC:

AN:

113194

Hom.:

Cov.:

AF XY:

0.0000283

AC XY:

AN XY:

35330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000923

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000937

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000257

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2021

The c.298G>A (p.G100S) 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 298, causing the glycine (G) at amino acid position 100 to be replaced by a serine (S). 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

Benign

0.14

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.6

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0050

FATHMM_MKL

Benign

0.00089

LIST_S2

Benign

0.22

M_CAP

Benign

0.0045

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.55

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.65

REVEL

Benign

0.20

Sift

Benign

0.31

Sift4G

Benign

0.38

Polyphen

0.95

Vest4

0.098

MVP

0.076

ClinPred

0.063

GERP RS

-1.1

Varity_R

0.050

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