Variant 7-113084063-A-T 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.659T>A(p.Phe220Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GPR85
NM_001146267.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.51

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=0.3325594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR85	NM_001146267.2 linkuse as main transcript	c.659T>A	p.Phe220Tyr	missense_variant	3/3	ENST00000424100.2	NP_001139739.1	P60893A4D0T8Q8NEN2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GPR85	ENST00000424100.2 linkuse as main transcript	c.659T>A	p.Phe220Tyr	missense_variant	3/3	1	NM_001146267.2	ENSP00000396763.1	P60893
GPR85	ENST00000297146.7 linkuse as main transcript	c.659T>A	p.Phe220Tyr	missense_variant	3/3	1		ENSP00000297146.2	P60893
GPR85	ENST00000449591.2 linkuse as main transcript	c.659T>A	p.Phe220Tyr	missense_variant	2/2	1		ENSP00000401178.1	P60893
GPR85	ENST00000610164.1 linkuse as main transcript	n.659T>A		non_coding_transcript_exon_variant	2/3	5		ENSP00000476863.1	P60893

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251472

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-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 05, 2024

The c.659T>A (p.F220Y) alteration is located in exon 3 (coding exon 1) of the GPR85 gene. This alteration results from a T to A substitution at nucleotide position 659, causing the phenylalanine (F) at amino acid position 220 to be replaced by a tyrosine (Y). 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

0.20

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

T;T;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

.;.;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.2

L;L;L

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.34

N;N;N

REVEL

Benign

0.26

Sift

Benign

0.046

D;D;D

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

0.96

D;D;D

Vest4

0.40

MutPred

0.46

Gain of phosphorylation at F220 (P = 0.0524);Gain of phosphorylation at F220 (P = 0.0524);Gain of phosphorylation at F220 (P = 0.0524);

MVP

0.33

MPC

1.4

ClinPred

0.67

GERP RS

5.5

Varity_R

0.23

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over