rs149637884

Variant names:

• chr11-72095011-G-A
• rs149637884
• NM_145309.6:c.352G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-72095011-G-A
• chr11-72095011-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145309.6(LRRC51):​c.352G>A​(p.Gly118Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LRRC51 NM_145309.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.114317715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC51	NM_145309.6	c.352G>A	p.Gly118Arg	missense_variant	Exon 5 of 6	ENST00000289488.8	NP_660352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC51	ENST00000289488.8	c.352G>A	p.Gly118Arg	missense_variant	Exon 5 of 6	1	NM_145309.6	ENSP00000289488.2
LRTOMT	ENST00000307198.11	c.-52G>A		5_prime_UTR_variant	Exon 3 of 7	2		ENSP00000305742.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Benign	0.89
DEOGEN2	Benign	0.0072	T;T;T;T;.;.;T;.;.;.;T;.;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.91	.;.;.;.;.;.;.;D;D;D;D;.;D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.11	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M;M;M;.;M;M;M;M;.;M;.;.
PhyloP100		1.6
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.69	.;.;N;.;N;N;N;N;N;.;N;.;N
REVEL	Benign	0.12
Sift	Benign	0.17	.;.;T;.;T;T;T;T;T;.;T;.;T
Sift4G	Benign	0.50	.;.;T;.;T;T;T;T;T;T;T;.;T
Polyphen		0.010	B;B;B;B;B;.;B;.;B;B;B;.;.
Vest4		0.37, 0.37, 0.28, 0.15, 0.37, 0.38
MutPred		0.38		Gain of MoRF binding (P = 0.02);Gain of MoRF binding (P = 0.02);Gain of MoRF binding (P = 0.02);Gain of MoRF binding (P = 0.02);.;Gain of MoRF binding (P = 0.02);Gain of MoRF binding (P = 0.02);Gain of MoRF binding (P = 0.02);Gain of MoRF binding (P = 0.02);.;Gain of MoRF binding (P = 0.02);Gain of MoRF binding (P = 0.02);Gain of MoRF binding (P = 0.02);
MVP		0.48
ClinPred		0.10	T
GERP RS		3.2
Mutation Taster		=295/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs149637884; hg19: chr11-71806057;