3-120167199-G-C

Variant names:

• chr3-120167199-G-C
• rs779085583
• NM_153002.3:c.2278C>G

Variant summary

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

The NM_153002.3(GPR156):​c.2278C>G​(p.Arg760Gly) 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 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R760Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPR156 NM_153002.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

Genes affected

GPR156 (HGNC:20844): (G protein-coupled receptor 156) G protein-coupled receptors (GPCRs) are a large superfamily of cell surface receptors characterized by 7 helical transmembrane domains, together with N-terminal extracellular and C-terminal intracellular domains.[supplied by OMIM, Mar 2008]

LOC105374065 (HGNC:):

ACMG classification

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
GPR156	NM_153002.3	c.2278C>G	p.Arg760Gly	missense_variant	Exon 10 of 10	ENST00000464295.6	NP_694547.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR156	ENST00000464295.6	c.2278C>G	p.Arg760Gly	missense_variant	Exon 10 of 10	5	NM_153002.3	ENSP00000417261.1
GPR156	ENST00000461057.1	c.2266C>G	p.Arg756Gly	missense_variant	Exon 9 of 9	1		ENSP00000418758.1
GPR156	ENST00000495912.5	n.*1341C>G		non_coding_transcript_exon_variant	Exon 4 of 4	5		ENSP00000417191.1
GPR156	ENST00000495912.5	n.*1341C>G		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000417191.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251206 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135754

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461854 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T;.
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T;.;T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.57	D;D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.1	M;M;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.055	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.69
MutPred		0.45		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);.;
MVP		0.43
MPC		1.0
ClinPred		0.99	D
GERP RS		2.0
Varity_R		0.56
gMVP		0.59

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

Other links and lift over

dbSNP: rs779085583; hg19: chr3-119886046;