chr1-202276316-G-A

Variant names:

• chr1-202276316-G-A
• NM_001017403.2:c.439G>A

Variant summary

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

The NM_001017403.2(LGR6):​c.439G>A​(p.Ala147Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LGR6 NM_001017403.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.98
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.439G>A	p.Ala147Thr	missense	Exon 5 of 18	NP_001017403.1	Q9HBX8-3
	LGR6	NM_021636.3		c.283G>A	p.Ala95Thr	missense	Exon 5 of 18	NP_067649.2	Q9HBX8-2
	LGR6	NM_001017404.2		c.300-21192G>A		intron	N/A	NP_001017404.1	Q9HBX8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGR6	ENST00000367278.8	TSL:1 MANE Select	c.439G>A	p.Ala147Thr	missense	Exon 5 of 18	ENSP00000356247.3	Q9HBX8-3
	LGR6	ENST00000255432.11	TSL:1	c.283G>A	p.Ala95Thr	missense	Exon 5 of 18	ENSP00000255432.7	Q9HBX8-2
	LGR6	ENST00000439764.2	TSL:1	c.300-21192G>A		intron	N/A	ENSP00000387869.2	Q9HBX8-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.21	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.52	N
PhyloP100		10
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.80
MutPred		0.33		Loss of sheet (P = 0.0817)
MVP		0.89
MPC		0.91
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.50
gMVP		0.52
Mutation Taster		=23/77	disease causing

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

Other links and lift over

hg19: chr1-202245444;