Variant 7-113084531-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001146267.2(GPR85):c.191G>C(p.Cys64Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GPR85
NM_001146267.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.12

Variant links:

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]

GPR85 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2831396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR85	NM_001146267.2 linkuse as main transcript	c.191G>C	p.Cys64Ser	missense_variant	3/3	ENST00000424100.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR85	ENST00000424100.2 linkuse as main transcript	c.191G>C	p.Cys64Ser	missense_variant	3/3	1	NM_001146267.2	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459990

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726518

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2023

The c.191G>C (p.C64S) alteration is located in exon 3 (coding exon 1) of the GPR85 gene. This alteration results from a G to C substitution at nucleotide position 191, causing the cysteine (C) at amino acid position 64 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

0.19

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Benign

0.90

DEOGEN2

Benign

0.17

T;T;T;.;.

Eigen

Benign

-0.029

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.94

.;.;D;D;D

M_CAP

Benign

0.0067

MetaRNN

Benign

0.28

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

N;N;N;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.73

N;N;N;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.016

D;D;D;T;T

Sift4G

Uncertain

0.012

D;D;D;.;D

Polyphen

0.0010

B;B;B;.;.

Vest4

0.52

MutPred

0.57

Loss of stability (P = 0.2479);Loss of stability (P = 0.2479);Loss of stability (P = 0.2479);Loss of stability (P = 0.2479);Loss of stability (P = 0.2479);

MVP

0.31

MPC

0.73

ClinPred

0.95

GERP RS

5.7

Varity_R

0.31

gMVP

0.57

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over