11-72104998-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000307198.11(LRTOMT):c.69G>C(p.Leu23Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0394 in 1,550,840 control chromosomes in the GnomAD database, including 2,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.073 ( 652 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1938 hom. )

Consequence

LRTOMT
ENST00000307198.11 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.295

Publications

10 publications found

Variant links:

Genes affected

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 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 63
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LRTOMT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-72104998-G-C is Benign according to our data. Variant chr11-72104998-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 44042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.295 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
LRTOMT	NM_001145308.5 link	c.69G>C	p.Leu23Leu	synonymous_variant	Exon 4 of 7	NP_001138780.1	Q8WZ04-1
LRTOMT	NM_001145309.4 link	c.69G>C	p.Leu23Leu	synonymous_variant	Exon 6 of 9	NP_001138781.1	Q8WZ04-1
LRTOMT	NM_001145310.4 link	c.69G>C	p.Leu23Leu	synonymous_variant	Exon 6 of 9	NP_001138782.1	Q8WZ04-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRTOMT	ENST00000307198.11 link	c.69G>C	p.Leu23Leu	synonymous_variant	Exon 4 of 7	2		ENSP00000305742.7

Frequencies

GnomAD3 genomes

AF:

0.0732

AC:

11125

AN:

152068

Hom.:

651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.0426

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.0353

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0216

Gnomad OTH

AF:

0.0525

GnomAD2 exomes

AF:

0.0681

AC:

10519

AN:

154352

AF XY:

0.0674

show subpopulations

Gnomad AFR exome

AF:

0.134

Gnomad AMR exome

AF:

0.118

Gnomad ASJ exome

AF:

0.0426

Gnomad EAS exome

AF:

0.163

Gnomad FIN exome

AF:

0.0349

Gnomad NFE exome

AF:

0.0215

Gnomad OTH exome

AF:

0.0490

GnomAD4 exome

AF:

0.0357

AC:

49959

AN:

1398654

Hom.:

1938

Cov.:

AF XY:

0.0374

AC XY:

25770

AN XY:

689802

show subpopulations

African (AFR)

AF:

0.135

AC:

4249

AN:

31576

American (AMR)

AF:

0.121

AC:

4319

AN:

35644

Ashkenazi Jewish (ASJ)

AF:

0.0414

AC:

1042

AN:

25158

East Asian (EAS)

AF:

0.160

AC:

5695

AN:

35698

South Asian (SAS)

AF:

0.105

AC:

8303

AN:

79100

European-Finnish (FIN)

AF:

0.0322

AC:

1588

AN:

49264

Middle Eastern (MID)

AF:

0.0304

AC:

173

AN:

5696

European-Non Finnish (NFE)

AF:

0.0203

AC:

21945

AN:

1078548

Other (OTH)

AF:

0.0456

AC:

2645

AN:

57970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

2205

4410

6616

8821

11026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1078

2156

3234

4312

5390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0733

AC:

11149

AN:

152186

Hom.:

652

Cov.:

AF XY:

0.0774

AC XY:

5755

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.133

AC:

5510

AN:

41484

American (AMR)

AF:

0.142

AC:

2176

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0426

AC:

148

AN:

3472

East Asian (EAS)

AF:

0.156

AC:

807

AN:

5180

South Asian (SAS)

AF:

0.114

AC:

550

AN:

4822

European-Finnish (FIN)

AF:

0.0353

AC:

374

AN:

10602

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0216

AC:

1467

AN:

68018

Other (OTH)

AF:

0.0515

AC:

109

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

496

993

1489

1986

2482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0332

Hom.:

Bravo

AF:

0.0800

Asia WGS

AF:

0.120

AC:

420

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

May 09, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Leu23Leu in Exon 04 of LRTOMT: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 12.8% (90/702) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs12272086). -

not provided

Benign:3

Aug 10, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hearing loss, autosomal recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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