NM_153002.3:c.2089C>T

Variant names:

• chr3-120167388-G-A
• rs775719509
• NM_153002.3:c.2089C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153002.3(GPR156):​c.2089C>T​(p.Arg697Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000713 in 1,613,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000075 (0 hom.)
• Consequence: GPR156 NM_153002.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.575
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04807785).

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.2089C>T	p.Arg697Cys	missense	Exon 10 of 10	NP_694547.2	Q8NFN8-1
	GPR156	NM_001168271.2		c.2077C>T	p.Arg693Cys	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.2089C>T	p.Arg697Cys	missense	Exon 10 of 10	ENSP00000417261.1	Q8NFN8-1
	GPR156	ENST00000461057.1	TSL:1	c.2077C>T	p.Arg693Cys	missense	Exon 9 of 9	ENSP00000418758.1	Q8NFN8-2
	GPR156	ENST00000932328.1		c.2089C>T	p.Arg697Cys	missense	Exon 10 of 10	ENSP00000602387.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250604 AF XY: 0.0000148

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000746 AC: 109 AN: 1461030 Hom.: 0 Cov.: 30 AF XY: 0.0000716 AC XY: 52 AN XY: 726712

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000927 AC: 103 AN: 1111432

Other (OTH) AF: 0.0000994 AC: 6 AN: 60368

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152242 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74380

African (AFR) AF: 0.0000482 AC: 2 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.068
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.9
DANN	Benign	0.87
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		-0.57
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.0070
Sift	Benign	0.21	T
Sift4G	Benign	0.22	T
Polyphen		0.0	B
Vest4		0.057
MVP		0.030
MPC		0.32
ClinPred		0.022	T
GERP RS		-0.48
Varity_R		0.061
gMVP		0.18
Mutation Taster		=93/7	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: rs775719509; hg19: chr3-119886235; COSMIC: COSV59942238;