chrX-115189833-G-A

Position:

chrX-115189833-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000317135.13(LRCH2):c.350-1463C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000484 in 1,166,285 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 174 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 0.00027 ( 0 hom., 7 hem., cov: 26)

Exomes 𝑓: 0.00051 ( 0 hom. 167 hem. )

Consequence

LRCH2
ENST00000317135.13 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.364

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026307672).

BP6

Variant X-115189833-G-A is Benign according to our data. Variant chrX-115189833-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3152566.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBMXL3	NM_001145346.2 linkuse as main transcript	c.392G>A	p.Arg131His	missense_variant	1/1	ENST00000424776.5	NP_001138818.1
LRCH2	NM_020871.4 linkuse as main transcript	c.350-1463C>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.392G>A	p.Arg131His	missense_variant	1/1		NM_001145346.2	ENSP00000417451	P1
LRCH2	ENST00000317135.13 linkuse as main transcript	c.350-1463C>T		intron_variant		1	NM_020871.4	ENSP00000325091	P2	Q5VUJ6-1
LRCH2	ENST00000538422.2 linkuse as main transcript	c.350-1463C>T		intron_variant		1		ENSP00000439366	A2	Q5VUJ6-2

Frequencies

GnomAD3 genomes

AF:

0.000273

AC:

AN:

113496

Hom.:

Cov.:

AF XY:

0.000196

AC XY:

AN XY:

35632

show subpopulations

Gnomad AFR

AF:

0.000255

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000184

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000351

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000375

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000236

AC:

AN:

106110

Hom.:

AF XY:

0.000235

AC XY:

AN XY:

38354

show subpopulations

Gnomad AFR exome

AF:

0.000191

Gnomad AMR exome

AF:

0.000311

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000568

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000257

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000506

AC:

533

AN:

1052789

Hom.:

Cov.:

AF XY:

0.000485

AC XY:

167

AN XY:

344427

show subpopulations

Gnomad4 AFR exome

AF:

0.0000803

Gnomad4 AMR exome

AF:

0.000251

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000261

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000606

Gnomad4 OTH exome

AF:

0.000316

GnomAD4 genome

AF:

0.000273

AC:

AN:

113496

Hom.:

Cov.:

AF XY:

0.000196

AC XY:

AN XY:

35632

show subpopulations

Gnomad4 AFR

AF:

0.000255

Gnomad4 AMR

AF:

0.000184

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000351

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000375

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000498

Hom.:

Bravo

AF:

0.000276

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000692

AC:

ExAC

AF:

0.000127

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-1.1

CADD

Benign

3.7

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0071

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.32

M_CAP

Benign

0.00094

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.51

REVEL

Benign

0.042

Sift

Benign

0.21

Sift4G

Benign

0.61

Polyphen

0.0

Vest4

0.034

MVP

0.055

ClinPred

0.017

GERP RS

-0.63

Varity_R

0.024

gMVP

0.13

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