Genetic Variant GPR83:p.Ala394Thr (chr11-94380241-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016540.4(GPR83):c.1180G>A(p.Ala394Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,376,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A394V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

GPR83
NM_016540.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.255

Publications

0 publications found

Variant links:

Genes affected

GPR83 (HGNC:4523): (G protein-coupled receptor 83) Predicted to enable neuropeptide receptor activity. Predicted to be involved in neuropeptide signaling pathway. Predicted to act upstream of or within response to glucocorticoid. Located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

GPR83 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.076156676).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016540.4. 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
	GPR83	NM_016540.4	MANE Select	c.1180G>A	p.Ala394Thr	missense	Exon 4 of 4	NP_057624.3
	GPR83	NM_001330345.2		c.1054G>A	p.Ala352Thr	missense	Exon 3 of 3	NP_001317274.1	Q9NYM4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR83	ENST00000243673.7	TSL:1 MANE Select	c.1180G>A	p.Ala394Thr	missense	Exon 4 of 4	ENSP00000243673.2	Q9NYM4-1
	GPR83	ENST00000539203.2	TSL:5	c.1054G>A	p.Ala352Thr	missense	Exon 3 of 3	ENSP00000441550.1	Q9NYM4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1376148

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

675452

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30564

American (AMR)

AF:

0.00

AC:

AN:

30992

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20290

East Asian (EAS)

AF:

0.00

AC:

AN:

39030

South Asian (SAS)

AF:

0.00

AC:

AN:

71302

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50194

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5344

European-Non Finnish (NFE)

AF:

0.00000187

AC:

AN:

1071824

Other (OTH)

AF:

0.00

AC:

AN:

56608

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.066

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.76

M_CAP

Benign

0.015

MetaRNN

Benign

0.076

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

0.26

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.55

REVEL

Benign

0.066

Sift

Benign

0.58

Sift4G

Benign

0.58

Polyphen

0.0

Vest4

0.018

MutPred

0.13

Gain of phosphorylation at A394 (P = 0.0423)

MVP

0.58

MPC

0.045

ClinPred

0.041

GERP RS

1.5

Varity_R

0.068

gMVP

0.42

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over