11-72089120-G-A

Position:

• chr11-72089120-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_145309.6(LRRC51):​c.37G>A​(p.Glu13Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00701 in 1,614,088 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0072 (50 hom.)
• Consequence: LRRC51 NM_145309.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.22

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:):

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007390946).
• BP6: Variant 11-72089120-G-A is Benign according to our data. Variant chr11-72089120-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642116.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC51	NM_145309.6	c.37G>A	p.Glu13Lys	missense_variant	3/6	ENST00000289488.8
LRTOMT	NM_001145309.4	c.-367G>A		5_prime_UTR_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC51	ENST00000289488.8	c.37G>A	p.Glu13Lys	missense_variant	3/6	1	NM_145309.6	P1

Frequencies

GnomAD3 genomes AF: 0.00494 AC: 751 AN: 152110 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00574

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00735

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00463 AC: 1165 AN: 251474 Hom.: 2 AF XY: 0.00486 AC XY: 660 AN XY: 135910

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00211

Gnomad ASJ exome AF: 0.0115

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000980

Gnomad FIN exome AF: 0.00397

Gnomad NFE exome AF: 0.00704

Gnomad OTH exome AF: 0.00652

GnomAD4 exome AF: 0.00722 AC: 10561 AN: 1461860 Hom.: 50 Cov.: 31 AF XY: 0.00711 AC XY: 5169 AN XY: 727230

Gnomad4 AFR exome AF: 0.00137

Gnomad4 AMR exome AF: 0.00237

Gnomad4 ASJ exome AF: 0.0129

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00103

Gnomad4 FIN exome AF: 0.00408

Gnomad4 NFE exome AF: 0.00838

Gnomad4 OTH exome AF: 0.00732

GnomAD4 genome AF: 0.00493 AC: 750 AN: 152228 Hom.: 2 Cov.: 32 AF XY: 0.00466 AC XY: 347 AN XY: 74440

Gnomad4 AFR AF: 0.00144

Gnomad4 AMR AF: 0.00393

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00574

Gnomad4 NFE AF: 0.00735

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00674 Hom.: 10

Bravo AF: 0.00465

TwinsUK AF: 0.00809 AC: 30

ALSPAC AF: 0.00727 AC: 28

ESP6500AA AF: 0.000682 AC: 3

ESP6500EA AF: 0.00629 AC: 54

ExAC AF: 0.00481 AC: 584

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00703

EpiControl AF: 0.00634

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

LRTOMT: BS1:Supporting, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.019	T;T;T;T;.;T;.;.;.;T;.;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	.;.;.;.;.;.;D;D;D;D;.;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.0074	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;M;M;M;M;M;M;.;M;M;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;N;N;N;N;N;N;N;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.1	N;.;N;.;N;N;N;N;N;N;.;N
REVEL	Benign	0.080
Sift	Benign	0.074	T;.;T;.;T;T;T;T;D;D;.;T
Sift4G	Benign	0.25	T;.;T;.;T;T;T;T;T;T;.;T
Polyphen		0.80	P;P;P;P;.;P;.;.;P;P;.;.
Vest4		0.60, 0.54, 0.59, 0.52
MVP		0.55
ClinPred		0.023	T
GERP RS		4.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs146942815; hg19: chr11-71800166;