11-72088834-A-G

Variant names:

• chr11-72088834-A-G
• rs150325419
• NM_145309.6:c.-55-195A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_145309.6(LRRC51):​c.-55-195A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 585,952 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00062 (0 hom.)
• Consequence: LRRC51 NM_145309.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.125
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-72088834-A-G is Benign according to our data. Variant chr11-72088834-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1202287.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC51	NM_145309.6	c.-55-195A>G		intron_variant	Intron 2 of 5	ENST00000289488.8	NP_660352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC51	ENST00000289488.8	c.-55-195A>G		intron_variant	Intron 2 of 5	1	NM_145309.6	ENSP00000289488.2
LRTOMT	ENST00000307198.11	c.-321-4662A>G		intron_variant	Intron 1 of 6	2		ENSP00000305742.7

Frequencies

GnomAD3 genomes AF: 0.00391 AC: 595 AN: 152180 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.000618 AC: 268 AN: 433654 Hom.: 0 Cov.: 6 AF XY: 0.000468 AC XY: 107 AN XY: 228798

African (AFR) AF: 0.0157 AC: 188 AN: 11982

American (AMR) AF: 0.00139 AC: 24 AN: 17318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12476

East Asian (EAS) AF: 0.00 AC: 0 AN: 26560

South Asian (SAS) AF: 0.000110 AC: 5 AN: 45620

European-Finnish (FIN) AF: 0.0000420 AC: 1 AN: 23784

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1810

European-Non Finnish (NFE) AF: 0.0000593 AC: 16 AN: 269942

Other (OTH) AF: 0.00141 AC: 34 AN: 24162

GnomAD4 genome AF: 0.00391 AC: 595 AN: 152298 Hom.: 1 Cov.: 32 AF XY: 0.00385 AC XY: 287 AN XY: 74464

African (AFR) AF: 0.0135 AC: 559 AN: 41554

American (AMR) AF: 0.00118 AC: 18 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68030

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00105 Hom.: 0

Bravo AF: 0.00438

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 28, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.0
DANN	Benign	0.58
PhyloP100		0.13

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: rs150325419; hg19: chr11-71799880;