rs12272086

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001145308.5(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
NM_001145308.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.295

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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

GnomAD3 exomes

AF:

0.0681

AC:

10519

AN:

154352

Hom.:

604

AF XY:

0.0674

AC XY:

5511

AN XY:

81818

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 SAS exome

AF:

0.105

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

Gnomad4 AFR exome

AF:

0.135

Gnomad4 AMR exome

AF:

0.121

Gnomad4 ASJ exome

AF:

0.0414

Gnomad4 EAS exome

AF:

0.160

Gnomad4 SAS exome

AF:

0.105

Gnomad4 FIN exome

AF:

0.0322

Gnomad4 NFE exome

AF:

0.0203

Gnomad4 OTH exome

AF:

0.0456

GnomAD4 genome

AF:

0.0733

AC:

11149

AN:

152186

Hom.:

652

Cov.:

AF XY:

0.0774

AC XY:

5755

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.133

Gnomad4 AMR

AF:

0.142

Gnomad4 ASJ

AF:

0.0426

Gnomad4 EAS

AF:

0.156

Gnomad4 SAS

AF:

0.114

Gnomad4 FIN

AF:

0.0353

Gnomad4 NFE

AF:

0.0216

Gnomad4 OTH

AF:

0.0515

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

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). -

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. -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

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

DANN

Uncertain

0.98

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