chr15-39801982-C-G

Variant names:

• chr15-39801982-C-G
• rs372306694
• NM_007223.3:c.698G>C

Variant summary

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

The NM_007223.3(GPR176):​c.698G>C​(p.Ser233Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR176 NM_007223.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

Genes affected

GPR176 (HGNC:32370): (G protein-coupled receptor 176) Members of the G protein-coupled receptor family, such as GPR176, are cell surface receptors involved in responses to hormones, growth factors, and neurotransmitters (Hata et al., 1995 [PubMed 7893747]).[supplied by OMIM, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007223.3. 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
	GPR176	NM_007223.3	MANE Select	c.698G>C	p.Ser233Thr	missense	Exon 3 of 3	NP_009154.1	Q14439-1
	GPR176	NM_001271854.2		c.695G>C	p.Ser232Thr	missense	Exon 4 of 4	NP_001258783.1	Q14439-3
	GPR176	NM_001271855.2		c.563G>C	p.Ser188Thr	missense	Exon 3 of 3	NP_001258784.1	Q14439-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR176	ENST00000561100.2	TSL:1 MANE Select	c.698G>C	p.Ser233Thr	missense	Exon 3 of 3	ENSP00000453076.1	Q14439-1
	GPR176	ENST00000299092.4	TSL:1	c.695G>C	p.Ser232Thr	missense	Exon 4 of 4	ENSP00000299092.3	Q14439-3
	GPR176	ENST00000543580.7	TSL:2	c.563G>C	p.Ser188Thr	missense	Exon 3 of 3	ENSP00000439361.1	Q14439-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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	0.11
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.9
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.24
Sift	Benign	0.22	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.61
MutPred		0.54		Loss of disorder (P = 0.0591)
MVP		0.67
MPC		1.2
ClinPred		0.79	D
GERP RS		5.9
Varity_R		0.16
gMVP		0.63

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: rs372306694; hg19: chr15-40094183;