Variant 12-71524474-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003667.4(LGR5):c.353T>C(p.Val118Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,451,788 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LGR5
NM_003667.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11

Variant links:

Genes affected

LGR5 (HGNC:4504): (leucine rich repeat containing G protein-coupled receptor 5) The protein encoded by this gene is a leucine-rich repeat-containing receptor (LGR) and member of the G protein-coupled, 7-transmembrane receptor (GPCR) superfamily. The encoded protein is a receptor for R-spondins and is involved in the canonical Wnt signaling pathway. This protein plays a role in the formation and maintenance of adult intestinal stem cells during postembryonic development. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

LGR5 links:

LGR5 (HGNC:):

LGR5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGR5	NM_003667.4 linkuse as main transcript	c.353T>C	p.Val118Ala	missense_variant	3/18	ENST00000266674.10	NP_003658.1	O75473-1A0A0A8K8C7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LGR5	ENST00000266674.10 linkuse as main transcript	c.353T>C	p.Val118Ala	missense_variant	3/18	1	NM_003667.4	ENSP00000266674.4	O75473-1
LGR5	ENST00000540815.2 linkuse as main transcript	c.353T>C	p.Val118Ala	missense_variant	3/17	1		ENSP00000441035.2	O75473-2
LGR5	ENST00000536515.5 linkuse as main transcript	c.353T>C	p.Val118Ala	missense_variant	3/17	1		ENSP00000443033.1	O75473-3
LGR5	ENST00000550851.5 linkuse as main transcript	n.450T>C		non_coding_transcript_exon_variant	3/20	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249826

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135052

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1451788

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722874

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.06e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 11, 2024

The c.353T>C (p.V118A) alteration is located in exon 3 (coding exon 3) of the LGR5 gene. This alteration results from a T to C substitution at nucleotide position 353, causing the valine (V) at amino acid position 118 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;.;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.86

D;T;T

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.67

D;D;D

MetaSVM

Benign

-0.58

MutationAssessor

Benign

0.65

N;N;N

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.9

D;N;D

REVEL

Benign

0.25

Sift

Uncertain

0.013

D;T;D

Sift4G

Benign

0.083

T;T;T

Polyphen

0.99

D;.;P

Vest4

0.84

MutPred

0.39

Gain of catalytic residue at Y114 (P = 0.0046);Gain of catalytic residue at Y114 (P = 0.0046);Gain of catalytic residue at Y114 (P = 0.0046);

MVP

0.89

MPC

0.36

ClinPred

0.70

GERP RS

5.3

Varity_R

0.59

gMVP

0.40

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over