NM_145309.6:c.83-29G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_145309.6(LRRC51):c.83-29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 1,588,678 control chromosomes in the GnomAD database, including 6,427 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.11 ( 1271 hom., cov: 32)

Exomes 𝑓: 0.071 ( 5156 hom. )

Consequence

LRRC51
NM_145309.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0960

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-72093467-G-A is Benign according to our data. Variant chr11-72093467-G-A is described in ClinVar as [Benign]. Clinvar id is 682806.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC51	NM_145309.6 link	c.83-29G>A		intron_variant	Intron 3 of 5	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.83-29G>A		intron_variant	Intron 3 of 5	1	NM_145309.6	ENSP00000289488.2		Q96E66-1
LRTOMT	ENST00000307198.11 link	c.-321-29G>A		intron_variant	Intron 1 of 6	2		ENSP00000305742.7

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17314

AN:

152066

Hom.:

1270

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.0899

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.0682

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0549

Gnomad OTH

AF:

0.0966

GnomAD3 exomes

AF:

0.106

AC:

22665

AN:

214540

Hom.:

1575

AF XY:

0.104

AC XY:

11994

AN XY:

115406

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.139

Gnomad ASJ exome

AF:

0.0934

Gnomad EAS exome

AF:

0.238

Gnomad SAS exome

AF:

0.154

Gnomad FIN exome

AF:

0.0734

Gnomad NFE exome

AF:

0.0562

Gnomad OTH exome

AF:

0.0872

GnomAD4 exome

AF:

0.0706

AC:

101401

AN:

1436492

Hom.:

5156

Cov.:

AF XY:

0.0728

AC XY:

51892

AN XY:

712696

show subpopulations

Gnomad4 AFR exome

AF:

0.189

Gnomad4 AMR exome

AF:

0.145

Gnomad4 ASJ exome

AF:

0.0900

Gnomad4 EAS exome

AF:

0.224

Gnomad4 SAS exome

AF:

0.155

Gnomad4 FIN exome

AF:

0.0702

Gnomad4 NFE exome

AF:

0.0513

Gnomad4 OTH exome

AF:

0.0832

GnomAD4 genome

AF:

0.114

AC:

17342

AN:

152186

Hom.:

1271

Cov.:

AF XY:

0.119

AC XY:

8843

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.185

Gnomad4 AMR

AF:

0.172

Gnomad4 ASJ

AF:

0.0899

Gnomad4 EAS

AF:

0.231

Gnomad4 SAS

AF:

0.161

Gnomad4 FIN

AF:

0.0682

Gnomad4 NFE

AF:

0.0550

Gnomad4 OTH

AF:

0.0946

Alfa

AF:

0.0815

Hom.:

157

Bravo

AF:

0.122

Asia WGS

AF:

0.177

AC:

618

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 16, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.9

DANN

Benign

0.54

BranchPoint Hunter

0.0

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