Variant 3-197817211-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001365715.1(LRCH3):c.443G>A(p.Cys148Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00141 in 1,606,238 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00094 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 3 hom. )

Consequence

LRCH3
NM_001365715.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.54

Variant links:

Genes affected

LRCH3 (HGNC:28637): (leucine rich repeats and calponin homology domain containing 3) Involved in septin cytoskeleton organization. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LRCH3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.120919704).

BP6

Variant 3-197817211-G-A is Benign according to our data. Variant chr3-197817211-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3033723.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRCH3	NM_001365715.1 linkuse as main transcript	c.443G>A	p.Cys148Tyr	missense_variant	3/21	ENST00000425562.7	NP_001352644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRCH3	ENST00000425562.7 linkuse as main transcript	c.443G>A	p.Cys148Tyr	missense_variant	3/21	5	NM_001365715.1	ENSP00000393579	P2	Q96II8-1

Frequencies

GnomAD3 genomes

AF:

0.000936

AC:

142

AN:

151754

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000315

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000790

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:

0.00169

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000640

AC:

156

AN:

243592

Hom.:

AF XY:

0.000652

AC XY:

AN XY:

131944

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000400

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000576

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00124

Gnomad OTH exome

AF:

0.000685

GnomAD4 exome

AF:

0.00146

AC:

2125

AN:

1454368

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

1014

AN XY:

723566

show subpopulations

Gnomad4 AFR exome

AF:

0.0000608

Gnomad4 AMR exome

AF:

0.000435

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.0000563

Gnomad4 NFE exome

AF:

0.00181

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.000935

AC:

142

AN:

151870

Hom.:

Cov.:

AF XY:

0.000687

AC XY:

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.000314

Gnomad4 AMR

AF:

0.000789

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00169

Gnomad4 OTH

AF:

0.000950

Alfa

AF:

0.00126

Hom.:

Bravo

AF:

0.000952

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000593

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LRCH3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 10, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

.;.;.;.;T

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.95

.;D;D;D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L;L;L;L

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-7.4

D;.;D;D;D

REVEL

Benign

0.24

Sift

Uncertain

0.015

D;.;D;D;D

Sift4G

Benign

0.15

T;.;T;T;T

Polyphen

1.0

D;D;.;D;.

Vest4

0.80

MVP

0.58

MPC

0.68

ClinPred

0.17

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.78

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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