NM_001017403.2:c.107C>T

Variant summary

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

The NM_001017403.2(LGR6):​c.107C>T​(p.Pro36Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000287 in 1,535,712 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

LGR6
NM_001017403.2 missense

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.17
Variant links:
Genes affected
LGR6 (HGNC:19719): (leucine rich repeat containing G protein-coupled receptor 6) This gene encodes a member of the leucine-rich repeat-containing subgroup of the G protein-coupled 7-transmembrane protein superfamily. The encoded protein is a glycoprotein hormone receptor with a large N-terminal extracellular domain that contains leucine-rich repeats important for the formation of a horseshoe-shaped interaction motif for ligand binding. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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 rank MANE Protein UniProt
LGR6NM_001017403.2 linkc.107C>T p.Pro36Leu missense_variant Exon 1 of 18 ENST00000367278.8 NP_001017403.1 Q9HBX8-3
LGR6XM_047426928.1 linkc.107C>T p.Pro36Leu missense_variant Exon 1 of 17 XP_047282884.1
LGR6XM_047426929.1 linkc.107C>T p.Pro36Leu missense_variant Exon 1 of 16 XP_047282885.1
LGR6XM_047426931.1 linkc.107C>T p.Pro36Leu missense_variant Exon 1 of 17 XP_047282887.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LGR6ENST00000367278.8 linkc.107C>T p.Pro36Leu missense_variant Exon 1 of 18 1 NM_001017403.2 ENSP00000356247.3 Q9HBX8-3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152154
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000905
AC:
15
AN:
165810
Hom.:
1
AF XY:
0.0000528
AC XY:
5
AN XY:
94724
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000394
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:
0.000117
Gnomad OTH exome
AF:
0.00129
GnomAD4 exome
AF:
0.0000296
AC:
41
AN:
1383558
Hom.:
0
Cov.:
32
AF XY:
0.0000247
AC XY:
17
AN XY:
687376
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000274
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000213
Gnomad4 NFE exome
AF:
0.0000148
Gnomad4 OTH exome
AF:
0.000280
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152154
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ExAC
AF:
0.000148
AC:
17

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.107C>T (p.P36L) alteration is located in exon 1 (coding exon 1) of the LGR6 gene. This alteration results from a C to T substitution at nucleotide position 107, causing the proline (P) at amino acid position 36 to be replaced by a leucine (L). 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
Benign
0.21
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.56
D
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.61
T
M_CAP
Pathogenic
0.62
D
MetaRNN
Uncertain
0.72
D
MetaSVM
Uncertain
0.29
D
MutationAssessor
Pathogenic
3.2
M
PrimateAI
Pathogenic
0.80
T
PROVEAN
Pathogenic
-5.5
D
REVEL
Uncertain
0.48
Sift
Uncertain
0.014
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.38
MutPred
0.54
Gain of stability (P = 0.0144);
MVP
0.87
MPC
0.27
ClinPred
0.76
D
GERP RS
3.9
Varity_R
0.37
gMVP
0.46

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.

Other links and lift over

dbSNP: rs772335116; hg19: chr1-202163224; API