Variant chr12-58877834-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The ENST00000320743.8(LRIG3):c.2102G>T(p.Arg701Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000439 in 1,594,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R701W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LRIG3
ENST00000320743.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.81

Variant links:

Genes affected

LRIG3 (HGNC:30991): (leucine rich repeats and immunoglobulin like domains 3) Predicted to act upstream of or within otolith morphogenesis. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

LRIG3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.779

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRIG3	NM_153377.5 linkuse as main transcript	c.2102G>T	p.Arg701Leu	missense_variant	15/19	ENST00000320743.8	NP_700356.2	Q6UXM1-1
LRIG3	NM_001136051.3 linkuse as main transcript	c.1922G>T	p.Arg641Leu	missense_variant	15/19		NP_001129523.1	Q6UXM1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRIG3	ENST00000320743.8 linkuse as main transcript	c.2102G>T	p.Arg701Leu	missense_variant	15/19	1	NM_153377.5	ENSP00000326759.3	Q6UXM1-1
LRIG3	ENST00000379141.8 linkuse as main transcript	c.1922G>T	p.Arg641Leu	missense_variant	15/19	1		ENSP00000368436.4	Q6UXM1-2
LRIG3	ENST00000433272.6 linkuse as main transcript	n.*340G>T		non_coding_transcript_exon_variant	16/20	1		ENSP00000413143.2	C9K080
LRIG3	ENST00000433272.6 linkuse as main transcript	n.*340G>T		3_prime_UTR_variant	16/20	1		ENSP00000413143.2	C9K080

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

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

GnomAD3 exomes

AF:

0.00000814

AC:

AN:

245802

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132820

show subpopulations

Gnomad AFR exome

AF:

0.000124

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1442306

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713820

show subpopulations

Gnomad4 AFR exome

AF:

0.0000915

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152014

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

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

Sep 01, 2021

The c.2102G>T (p.R701L) alteration is located in exon 15 (coding exon 15) of the LRIG3 gene. This alteration results from a G to T substitution at nucleotide position 2102, causing the arginine (R) at amino acid position 701 to be replaced by a leucine (L). 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

Uncertain

0.43

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

.;T

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.041

MetaRNN

Pathogenic

0.78

D;D

MetaSVM

Benign

-0.43

MutationAssessor

Benign

0.91

.;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-2.9

D;D

REVEL

Uncertain

0.55

Sift

Uncertain

0.019

D;D

Sift4G

Benign

0.070

T;T

Polyphen

0.95

P;D

Vest4

0.86

MVP

0.75

MPC

0.81

ClinPred

0.92

GERP RS

5.9

Varity_R

0.24

gMVP

0.67

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