rs146942815

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_145309.6(LRRC51):c.37G>A(p.Glu13Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00701 in 1,614,088 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0072 ( 50 hom. )

Consequence

LRRC51
NM_145309.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.22

Publications

13 publications found

Variant links:

Genes affected

LRRC51 (HGNC:55526): (leucine rich repeat containing 51) This gene belongs to the leucine-rich repeat containing family. The encoded protein contains a transmembrane domain and two leucine-rich repeat domains. Unlike in mouse and other mammals, readthrough transcription is observed in primates between this gene and the adjacent transmembrane O-methyltransferase (Tomt) gene. Previously, this locus was annotated as a single gene representing the readthrough transcripts as well as the two different transcript species that encoded different proteins. It has since been split into three genes, including the two stand-alone genes and a third gene representing the readthrough transcription. [provided by RefSeq, Feb 2022]

LRRC51 links:

LRTOMT (HGNC:25033): (leucine rich transmembrane and O-methyltransferase domain containing) This locus represents naturally occurring readthrough transcription between the neighboring LRRC51 (leucine-rich repeat containing 51) and TOMT (transmembrane O-methyltransferase) genes on chromosome 11. The readthrough transcript encodes a fusion protein that shares sequence identity with each individual gene product. Multiple reports implicate mutations in this gene in nonsyndromic deafness.[provided by RefSeq, Feb 2021]

LRTOMT links:

LAMTOR1 (HGNC:26068): (late endosomal/lysosomal adaptor, MAPK and MTOR activator 1) Enables GTPase binding activity. Contributes to guanyl-nucleotide exchange factor activity and molecular adaptor activity. Involved in several processes, including cholesterol homeostasis; positive regulation of TOR signaling; and regulation of cholesterol transport. Located in lysosome. Part of Ragulator complex. [provided by Alliance of Genome Resources, Apr 2022]

LAMTOR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007390946).

BP6

Variant 11-72089120-G-A is Benign according to our data. Variant chr11-72089120-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642116.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC51	NM_145309.6 link	c.37G>A	p.Glu13Lys	missense_variant	Exon 3 of 6	ENST00000289488.8	NP_660352.1	Q96E66-1A0A024R5L6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC51	ENST00000289488.8 link	c.37G>A	p.Glu13Lys	missense_variant	Exon 3 of 6	1	NM_145309.6	ENSP00000289488.2		Q96E66-1
LRTOMT	ENST00000307198.11 link	c.-321-4376G>A		intron_variant	Intron 1 of 6	2		ENSP00000305742.7

Frequencies

GnomAD3 genomes

AF:

0.00494

AC:

751

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00574

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00735

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00463

AC:

1165

AN:

251474

AF XY:

0.00486

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00211

Gnomad ASJ exome

AF:

0.0115

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00397

Gnomad NFE exome

AF:

0.00704

Gnomad OTH exome

AF:

0.00652

GnomAD4 exome

AF:

0.00722

AC:

10561

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00711

AC XY:

5169

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

33480

American (AMR)

AF:

0.00237

AC:

106

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0129

AC:

338

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00103

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00408

AC:

218

AN:

53416

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00838

AC:

9314

AN:

1111986

Other (OTH)

AF:

0.00732

AC:

442

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

598

1196

1794

2392

2990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00493

AC:

750

AN:

152228

Hom.:

Cov.:

AF XY:

0.00466

AC XY:

347

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00144

AC:

AN:

41526

American (AMR)

AF:

0.00393

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0130

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00104

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00574

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00735

AC:

500

AN:

68006

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

127

170

212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00636

Hom.:

Bravo

AF:

0.00465

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00629

AC:

ExAC

AF:

0.00481

AC:

584

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00703

EpiControl

AF:

0.00634

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

LRTOMT: BS1:Supporting, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.019

T;T;T;T;.;T;.;.;.;T;.;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

.;.;.;.;.;.;D;D;D;D;.;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.0074

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;M;M;M;M;M;M;.;M;M;.;.

PhyloP100

5.2

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.1

N;.;N;.;N;N;N;N;N;N;.;N

REVEL

Benign

0.080

Sift

Benign

0.074

T;.;T;.;T;T;T;T;D;D;.;T

Sift4G

Benign

0.25

T;.;T;.;T;T;T;T;T;T;.;T

Polyphen

0.80

P;P;P;P;.;P;.;.;P;P;.;.

Vest4

0.60, 0.54, 0.59, 0.52

MVP

0.55

ClinPred

0.023

GERP RS

4.8

Mutation Taster

=280/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs146942815

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over