rs116078212

Variant names:

• chr11-72088556-C-T
• rs116078212
• NM_145309.6:c.-56+176C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_145309.6(LRRC51):​c.-56+176C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 623,644 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (2 hom.)
• Consequence: LRRC51 NM_145309.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0600
• 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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-72088556-C-T is Benign according to our data. Variant chr11-72088556-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1196077.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 gene

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.-56+176C>T		intron	N/A	NP_660352.1	Q96E66-1
	LRTOMT	NM_001145308.5		c.-321-4940C>T		intron	N/A	NP_001138780.1
	LRTOMT	NM_001145309.4		c.-459+176C>T		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.-56+176C>T		intron	N/A	ENSP00000289488.2	Q96E66-1
	LRTOMT	ENST00000307198.11	TSL:2	c.-321-4940C>T		intron	N/A	ENSP00000305742.7
	LRRC51	ENST00000541614.5	TSL:1	c.-56+176C>T		intron	N/A	ENSP00000438522.1	Q96E66-2

Frequencies

GnomAD3 genomes AF: 0.00372 AC: 566 AN: 152178 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.000443 AC: 209 AN: 471348 Hom.: 2 Cov.: 0 AF XY: 0.000359 AC XY: 90 AN XY: 250404

African (AFR) AF: 0.0132 AC: 178 AN: 13520

American (AMR) AF: 0.000359 AC: 9 AN: 25076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15228

East Asian (EAS) AF: 0.00 AC: 0 AN: 31074

South Asian (SAS) AF: 0.00 AC: 0 AN: 49100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2234

European-Non Finnish (NFE) AF: 0.00000720 AC: 2 AN: 277966

Other (OTH) AF: 0.000740 AC: 20 AN: 27028

GnomAD4 genome AF: 0.00372 AC: 567 AN: 152296 Hom.: 4 Cov.: 32 AF XY: 0.00379 AC XY: 282 AN XY: 74472

African (AFR) AF: 0.0132 AC: 548 AN: 41556

American (AMR) AF: 0.000916 AC: 14 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00291 Hom.: 0

Bravo AF: 0.00420

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.9
DANN	Benign	0.49
PhyloP100		0.060
PromoterAI		-0.022	Neutral
Mutation Taster		=100/0	polymorphism

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: rs116078212; hg19: chr11-71799602;