chr7-113084362-A-T

Variant names:

• chr7-113084362-A-T
• rs2256044
• NM_001146267.2:c.360T>A

Variant summary

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

The NM_001146267.2(GPR85):​c.360T>A​(p.Tyr120*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GPR85 NM_001146267.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.87
• Publications: 15 publications found

Genes affected

GPR85 (HGNC:4536): (G protein-coupled receptor 85) Members of the G protein-coupled receptor (GPCR) family, such as GPR85, have a similar structure characterized by 7 transmembrane domains. Activation of GPCRs by extracellular stimuli, such as neurotransmitters, hormones, or light, induces an intracellular signaling cascade mediated by heterotrimeric GTP-binding proteins, or G proteins (Matsumoto et al., 2000 [PubMed 10833454]).[supplied by OMIM, Aug 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_001146267.2. 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
	GPR85	NM_001146267.2	MANE Select	c.360T>A	p.Tyr120*	stop_gained	Exon 3 of 3	NP_001139739.1	P60893
	GPR85	NM_001146265.2		c.360T>A	p.Tyr120*	stop_gained	Exon 3 of 3	NP_001139737.1	A4D0T8
	GPR85	NM_001146266.2		c.360T>A	p.Tyr120*	stop_gained	Exon 2 of 2	NP_001139738.1	A4D0T8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR85	ENST00000424100.2	TSL:1 MANE Select	c.360T>A	p.Tyr120*	stop_gained	Exon 3 of 3	ENSP00000396763.1	P60893
	GPR85	ENST00000297146.7	TSL:1	c.360T>A	p.Tyr120*	stop_gained	Exon 3 of 3	ENSP00000297146.2	P60893
	GPR85	ENST00000449591.2	TSL:1	c.360T>A	p.Tyr120*	stop_gained	Exon 2 of 2	ENSP00000401178.1	P60893

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461796 Hom.: 0 Cov.: 48 AF XY: 0.00 AC XY: 0 AN XY: 727214

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111920

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	38
DANN	Uncertain	0.99
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.94	D
PhyloP100		6.9
Vest4		0.60
GERP RS		5.7
Mutation Taster		=24/176	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: rs2256044; hg19: chr7-112724417;