NM_001393907.1:c.418C>A

Variant names:

• chr1-109543440-C-A
• rs1437368510
• NM_001393907.1:c.418C>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001393907.1(GPR61):​c.418C>A​(p.Arg140Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR61 NM_001393907.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.77
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.964

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.418C>A	p.Arg140Ser	missense	Exon 2 of 2	NP_001380836.1	Q9BZJ8
	GPR61	NM_031936.6		c.418C>A	p.Arg140Ser	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.418C>A	p.Arg140Ser	missense	Exon 2 of 2	ENSP00000432456.1	Q9BZJ8
	GPR61	ENST00000689084.1		c.418C>A	p.Arg140Ser	missense	Exon 2 of 3	ENSP00000509600.1	A0A8I5KY74
	GPR61	ENST00000404129.6	TSL:5	n.418C>A		non_coding_transcript_exon	Exon 2 of 3	ENSP00000385422.2	Q9BZJ8

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	0.99
BayesDel_addAF	Pathogenic	0.54	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.36	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.6	H
PhyloP100		4.8
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-5.9	D
REVEL	Pathogenic	0.92
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.99
MutPred		0.83		Gain of catalytic residue at V138 (P = 0.2112)
MVP		1.0
MPC		1.7
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.97
gMVP		0.99
Mutation Taster		=21/79	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

dbSNP: rs1437368510; hg19: chr1-110086062;