dbSNP rs772335116: LGR6:p.Pro36Arg (chr1-202194096-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001017403.2(LGR6):c.107C>G(p.Pro36Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P36L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

LGR6
NM_001017403.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.17

Publications

0 publications found

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]

LGR6 links:

ENSG00000295211 (HGNC:):

ENSG00000295211 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.868

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017403.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGR6	NM_001017403.2	MANE Select	c.107C>G	p.Pro36Arg	missense	Exon 1 of 18	NP_001017403.1	Q9HBX8-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LGR6	ENST00000367278.8	TSL:1 MANE Select	c.107C>G	p.Pro36Arg	missense	Exon 1 of 18	ENSP00000356247.3	Q9HBX8-3
LGR6	ENST00000904634.1		c.107C>G	p.Pro36Arg	missense	Exon 1 of 19	ENSP00000574693.1
LGR6	ENST00000904651.1		c.107C>G	p.Pro36Arg	missense	Exon 1 of 19	ENSP00000574710.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000603

AC:

AN:

165810

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.23e-7

AC:

AN:

1383558

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

687376

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29110

American (AMR)

AF:

0.0000274

AC:

AN:

36518

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24406

East Asian (EAS)

AF:

0.00

AC:

AN:

33194

South Asian (SAS)

AF:

0.00

AC:

AN:

78596

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3976

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1082994

Other (OTH)

AF:

0.00

AC:

AN:

57234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.62

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.49

MetaRNN

Pathogenic

0.87

MetaSVM

Uncertain

0.42

MutationAssessor

Pathogenic

3.2

PhyloP100

3.2

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-4.8

REVEL

Uncertain

0.54

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.64

MutPred

0.56

Loss of glycosylation at P36 (P = 0.0214)

MVP

0.88

MPC

0.28

ClinPred

0.99

GERP RS

3.9

PromoterAI

0.030

Neutral

(source)

Varity_R

0.66

gMVP

0.49

Mutation Taster

=73/27

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over