NM_145309.6:c.289-256_289-255dupAG

Variant names:

• chr11-72094686-T-TGA
• rs34329029
• NM_145309.6:c.289-256_289-255dupAG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_145309.6(LRRC51):​c.289-256_289-255dupAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0935 in 722,600 control chromosomes in the GnomAD database, including 4,448 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1265 hom., cov: 30)
  • Exomes 𝑓: 0.088 (3183 hom.)
• Consequence: LRRC51 NM_145309.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.605
• Publications: 0 publications found

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]

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]

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]

ACMG classification

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

• BP6: Variant 11-72094686-T-TGA is Benign according to our data. Variant chr11-72094686-T-TGA is described in ClinVar as [Benign]. Clinvar id is 1258396.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC51	NM_145309.6	c.289-256_289-255dupAG		intron_variant	Intron 4 of 5	ENST00000289488.8	NP_660352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC51	ENST00000289488.8	c.289-256_289-255dupAG		intron_variant	Intron 4 of 5	1	NM_145309.6	ENSP00000289488.2
LRTOMT	ENST00000307198.11	c.-115-256_-115-255dupAG		intron_variant	Intron 2 of 6	2		ENSP00000305742.7

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17284 AN: 152030 Hom.: 1264 Cov.: 30

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0899

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0675

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0549

Gnomad OTH AF: 0.0966

GnomAD4 exome AF: 0.0881 AC: 50229 AN: 570452 Hom.: 3183 Cov.: 6 AF XY: 0.0904 AC XY: 27816 AN XY: 307572

African (AFR) AF: 0.180 AC: 2895 AN: 16126

American (AMR) AF: 0.146 AC: 5057 AN: 34712

Ashkenazi Jewish (ASJ) AF: 0.0895 AC: 1801 AN: 20126

East Asian (EAS) AF: 0.222 AC: 7151 AN: 32188

South Asian (SAS) AF: 0.154 AC: 9709 AN: 63100

European-Finnish (FIN) AF: 0.0689 AC: 2316 AN: 33628

Middle Eastern (MID) AF: 0.0785 AC: 302 AN: 3848

European-Non Finnish (NFE) AF: 0.0544 AC: 18242 AN: 335512

Other (OTH) AF: 0.0883 AC: 2756 AN: 31212

GnomAD4 genome AF: 0.114 AC: 17312 AN: 152148 Hom.: 1265 Cov.: 30 AF XY: 0.119 AC XY: 8825 AN XY: 74380

African (AFR) AF: 0.185 AC: 7677 AN: 41468

American (AMR) AF: 0.172 AC: 2634 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0899 AC: 312 AN: 3472

East Asian (EAS) AF: 0.229 AC: 1180 AN: 5162

South Asian (SAS) AF: 0.161 AC: 777 AN: 4818

European-Finnish (FIN) AF: 0.0675 AC: 716 AN: 10600

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0549 AC: 3734 AN: 68014

Other (OTH) AF: 0.0946 AC: 200 AN: 2114

Alfa AF: 0.0836 Hom.: 93

Bravo AF: 0.121

Asia WGS AF: 0.177 AC: 617 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 28, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs34329029; hg19: chr11-71805732; COSMIC: COSV107224826; COSMIC: COSV107224826;