3-120167211-A-C

Variant names:

• chr3-120167211-A-C
• rs1029465170
• NM_153002.3:c.2266T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153002.3(GPR156):​c.2266T>G​(p.Cys756Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. C756R) 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: 5.10
• Publications: 0 publications found

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]

GSK3B-DT (HGNC:55635): (GSK3B divergent transcript)

LOC105374065 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33001298).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153002.3. 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
	GPR156	NM_153002.3	MANE Select	c.2266T>G	p.Cys756Gly	missense	Exon 10 of 10	NP_694547.2	Q8NFN8-1
	GPR156	NM_001168271.2		c.2254T>G	p.Cys752Gly	missense	Exon 10 of 10	NP_001161743.1	Q8NFN8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR156	ENST00000464295.6	TSL:5 MANE Select	c.2266T>G	p.Cys756Gly	missense	Exon 10 of 10	ENSP00000417261.1	Q8NFN8-1
	GPR156	ENST00000461057.1	TSL:1	c.2254T>G	p.Cys752Gly	missense	Exon 9 of 9	ENSP00000418758.1	Q8NFN8-2
	GPR156	ENST00000932328.1		c.2266T>G	p.Cys756Gly	missense	Exon 10 of 10	ENSP00000602387.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.098	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.1
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.22
Sift	Benign	0.080	T
Sift4G	Benign	0.30	T
Polyphen		1.0	D
Vest4		0.53
MutPred		0.36		Loss of stability (P = 0.0105)
MVP		0.40
MPC		0.98
ClinPred		0.97	D
GERP RS		5.0
Varity_R		0.36
gMVP		0.37
Mutation Taster		=67/33	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: rs1029465170; hg19: chr3-119886058;