chr1-109543748-C-A

Variant names:

• chr1-109543748-C-A
• rs201122595
• NM_001393907.1:c.726C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393907.1(GPR61):​c.726C>A​(p.His242Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPR61 NM_001393907.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.46
• Publications: 0 publications found

Genes affected

GPR61 (HGNC:13300): (G protein-coupled receptor 61) This gene belongs to the G-protein coupled receptor 1 family. G protein-coupled receptors contain 7 transmembrane domains and transduce extracellular signals through heterotrimeric G proteins. The protein encoded by this gene is most closely related to biogenic amine receptors. [provided by RefSeq, Jul 2008]

ENSG00000254942 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07425833).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393907.1. 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
	GPR61	NM_001393907.1	MANE Select	c.726C>A	p.His242Gln	missense	Exon 2 of 2	NP_001380836.1	Q9BZJ8
	GPR61	NM_031936.6		c.726C>A	p.His242Gln	missense	Exon 2 of 3	NP_114142.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR61	ENST00000527748.5	TSL:2 MANE Select	c.726C>A	p.His242Gln	missense	Exon 2 of 2	ENSP00000432456.1	Q9BZJ8
	GPR61	ENST00000689084.1		c.453+273C>A		intron	N/A	ENSP00000509600.1	A0A8I5KY74
	GPR61	ENST00000404129.6	TSL:5	n.726C>A		non_coding_transcript_exon	Exon 2 of 3	ENSP00000385422.2	Q9BZJ8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460942 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726806

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60382

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	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.76
DANN	Benign	0.88
DEOGEN2	Benign	0.26	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.79	N
PhyloP100		-3.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.17
Sift	Benign	0.44	T
Sift4G	Benign	0.53	T
Polyphen		0.045	B
Vest4		0.084
MutPred		0.54		Gain of glycosylation at P244 (P = 0.0722)
MVP		0.26
MPC		0.66
ClinPred		0.40	T
GERP RS		-4.7
Varity_R		0.20
gMVP		0.38
Mutation Taster		=51/49	polymorphism

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

dbSNP: rs201122595; hg19: chr1-110086370; COSMIC: COSV100879808; COSMIC: COSV100879808;