chr12-71566909-T-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003667.4(LGR5):āc.1067T>Gā(p.Val356Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
LGR5
NM_003667.4 missense
NM_003667.4 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 6.00
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]
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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 | c.1067T>G | p.Val356Gly | missense_variant | 11/18 | ENST00000266674.10 | NP_003658.1 | |
LOC105369833 | XR_001749200.2 | n.118+4724A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LGR5 | ENST00000266674.10 | c.1067T>G | p.Val356Gly | missense_variant | 11/18 | 1 | NM_003667.4 | ENSP00000266674 | P1 | |
LGR5 | ENST00000540815.2 | c.995T>G | p.Val332Gly | missense_variant | 10/17 | 1 | ENSP00000441035 | |||
LGR5 | ENST00000536515.5 | c.851T>G | p.Val284Gly | missense_variant | 10/17 | 1 | ENSP00000443033 | |||
LGR5 | ENST00000550851.5 | n.1164T>G | non_coding_transcript_exon_variant | 11/20 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251222Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135780
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1457760Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 725492
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GnomAD4 genome Cov.: 32
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32
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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 | Jun 05, 2024 | The c.1067T>G (p.V356G) alteration is located in exon 11 (coding exon 11) of the LGR5 gene. This alteration results from a T to G substitution at nucleotide position 1067, causing the valine (V) at amino acid position 356 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
P;.;B
Vest4
MutPred
Gain of catalytic residue at P352 (P = 0.0159);.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at