chr11-72094686-TGAGA-T

Variant names:

• chr11-72094686-TGAGA-T
• rs34329029
• NM_145309.6:c.289-258_289-255delAGAG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145309.6(LRRC51):​c.289-258_289-255delAGAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000701 in 570,510 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: LRRC51 NM_145309.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.839
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145309.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC51	NM_145309.6	MANE Select	c.289-258_289-255delAGAG		intron	N/A	NP_660352.1	Q96E66-1
	LRTOMT	NM_001145308.5		c.-115-258_-115-255delAGAG		intron	N/A	NP_001138780.1
	LRTOMT	NM_001145309.4		c.-115-258_-115-255delAGAG		intron	N/A	NP_001138781.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC51	ENST00000289488.8	TSL:1 MANE Select	c.289-258_289-255delAGAG		intron	N/A	ENSP00000289488.2	Q96E66-1
	LRTOMT	ENST00000307198.11	TSL:2	c.-115-258_-115-255delAGAG		intron	N/A	ENSP00000305742.7
	LRRC51	ENST00000541614.5	TSL:1	c.289-258_289-255delAGAG		intron	N/A	ENSP00000438522.1	Q96E66-2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000701 AC: 4 AN: 570510 Hom.: 0 AF XY: 0.00000325 AC XY: 1 AN XY: 307608

African (AFR) AF: 0.00 AC: 0 AN: 16130

American (AMR) AF: 0.00 AC: 0 AN: 34714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20126

East Asian (EAS) AF: 0.00 AC: 0 AN: 32188

South Asian (SAS) AF: 0.00 AC: 0 AN: 63116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3854

European-Non Finnish (NFE) AF: 0.0000119 AC: 4 AN: 335540

Other (OTH) AF: 0.00 AC: 0 AN: 31212

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.84

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

Other links and lift over

dbSNP: rs34329029; hg19: chr11-71805732;