11-72088919-T-C

Variant names:

• chr11-72088919-T-C
• rs78796585
• NM_145309.6:c.-55-110T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145309.6(LRRC51):​c.-55-110T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00457 in 1,291,252 control chromosomes in the GnomAD database, including 211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (124 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (87 hom.)
• Consequence: LRRC51 NM_145309.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.115
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-72088919-T-C is Benign according to our data. Variant chr11-72088919-T-C is described in ClinVar as [Benign]. Clinvar id is 1247784.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC51	NM_145309.6	c.-55-110T>C		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.-55-110T>C		intron_variant	Intron 2 of 5	1	NM_145309.6	ENSP00000289488.2
LRTOMT	ENST00000307198.11	c.-321-4577T>C		intron_variant	Intron 1 of 6	2		ENSP00000305742.7

Frequencies

GnomAD3 genomes AF: 0.0216 AC: 3281 AN: 152072 Hom.: 124 Cov.: 32

Gnomad AFR AF: 0.0750

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0154

GnomAD4 exome AF: 0.00229 AC: 2613 AN: 1139062 Hom.: 87 Cov.: 14 AF XY: 0.00201 AC XY: 1150 AN XY: 572488

African (AFR) AF: 0.0787 AC: 2055 AN: 26098

American (AMR) AF: 0.00398 AC: 128 AN: 32160

Ashkenazi Jewish (ASJ) AF: 0.0000909 AC: 2 AN: 22012

East Asian (EAS) AF: 0.00 AC: 0 AN: 34450

South Asian (SAS) AF: 0.000220 AC: 16 AN: 72848

European-Finnish (FIN) AF: 0.0000277 AC: 1 AN: 36088

Middle Eastern (MID) AF: 0.00781 AC: 27 AN: 3458

European-Non Finnish (NFE) AF: 0.000138 AC: 119 AN: 862806

Other (OTH) AF: 0.00539 AC: 265 AN: 49142

GnomAD4 genome AF: 0.0216 AC: 3292 AN: 152190 Hom.: 124 Cov.: 32 AF XY: 0.0210 AC XY: 1565 AN XY: 74400

African (AFR) AF: 0.0750 AC: 3113 AN: 41506

American (AMR) AF: 0.00804 AC: 123 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

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

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10598

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68008

Other (OTH) AF: 0.0152 AC: 32 AN: 2106

Alfa AF: 0.0149 Hom.: 10

Bravo AF: 0.0249

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 17, 2018

GeneDx

Significance: 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	-0.80
CADD	Benign	6.8
DANN	Benign	0.60
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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: rs78796585; hg19: chr11-71799965;