Variant 12-122183253-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001098519.2(LRRC43):c.109A>C(p.Lys37Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000222 in 1,566,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

LRRC43
NM_001098519.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.351

Variant links:

Genes affected

LRRC43 (HGNC:28562): (leucine rich repeat containing 43)

LRRC43 links:

LRRC43 (HGNC:):

LRRC43 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.013702989).

BP6

Variant 12-122183253-A-C is Benign according to our data. Variant chr12-122183253-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2516465.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC43	NM_001098519.2 linkuse as main transcript	c.109A>C	p.Lys37Gln	missense_variant	1/12	ENST00000339777.5	NP_001091989.1	Q8N309-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRRC43	ENST00000339777.5 linkuse as main transcript	c.109A>C	p.Lys37Gln	missense_variant	1/12	5	NM_001098519.2	ENSP00000344233.4	Q8N309-1
LRRC43	ENST00000537729.5 linkuse as main transcript	c.-405-1266A>C		intron_variant		5		ENSP00000438751.1	F5H0N3
LRRC43	ENST00000541498.5 linkuse as main transcript	n.128A>C		non_coding_transcript_exon_variant	1/4	5
LRRC43	ENST00000537113.5 linkuse as main transcript	n.71+181A>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000232

AC:

AN:

185232

Hom.:

AF XY:

0.000200

AC XY:

AN XY:

104918

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:

0.000591

Gnomad NFE exome

AF:

0.000429

Gnomad OTH exome

AF:

0.000214

GnomAD4 exome

AF:

0.000235

AC:

332

AN:

1414678

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

144

AN XY:

703258

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:

0.000667

Gnomad4 NFE exome

AF:

0.000269

Gnomad4 OTH exome

AF:

0.000204

GnomAD4 genome

AF:

0.000105

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000171

Hom.:

Bravo

AF:

0.000125

ExAC

AF:

0.000311

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

May 31, 2023

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

0.081

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.8

DANN

Benign

0.56

DEOGEN2

Benign

0.00038

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.57

M_CAP

Benign

0.047

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.38

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.22

REVEL

Benign

0.024

Sift

Benign

0.68

Sift4G

Benign

0.61

Polyphen

0.0030

Vest4

0.080

MutPred

0.40

Gain of catalytic residue at L40 (P = 0.0021);

MVP

0.088

MPC

0.26

ClinPred

0.013

GERP RS

-0.71

Varity_R

0.063

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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