chr7-113083923-C-T

Position:

• chr7-113083923-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001146267.2(GPR85):​c.799G>A​(p.Gly267Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR85 NM_001146267.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.12

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24227071).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR85	NM_001146267.2	c.799G>A	p.Gly267Ser	missense_variant	3/3	ENST00000424100.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR85	ENST00000424100.2	c.799G>A	p.Gly267Ser	missense_variant	3/3	1	NM_001146267.2	P1
GPR85	ENST00000297146.7	c.799G>A	p.Gly267Ser	missense_variant	3/3	1		P1
GPR85	ENST00000449591.2	c.799G>A	p.Gly267Ser	missense_variant	2/2	1		P1
GPR85	ENST00000610164.1	c.799G>A	p.Gly267Ser	missense_variant, NMD_transcript_variant	2/3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 11, 2022

The c.799G>A (p.G267S) alteration is located in exon 3 (coding exon 1) of the GPR85 gene. This alteration results from a G to A substitution at nucleotide position 799, causing the glycine (G) at amino acid position 267 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T;T
Eigen	Benign	0.11
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.93	.;.;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	N;N;N
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.79	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.13	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.99	D;D;D
Vest4		0.055
MutPred		0.50		Gain of catalytic residue at G267 (P = 0.0058);Gain of catalytic residue at G267 (P = 0.0058);Gain of catalytic residue at G267 (P = 0.0058);
MVP		0.093
MPC		0.75
ClinPred		0.70	D
GERP RS		3.6
Varity_R		0.13
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-112723978;