rs143962803

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_000677.4(ADORA3):c.583G>A(p.Ala195Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000326 in 1,614,158 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

ADORA3
NM_000677.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.69

Variant links:

Genes affected

ADORA3 (HGNC:268): (adenosine A3 receptor) This gene encodes a protein that belongs to the family of adenosine receptors, which are G-protein-coupled receptors that are involved in a variety of intracellular signaling pathways and physiological functions. The receptor encoded by this gene mediates a sustained cardioprotective function during cardiac ischemia, it is involved in the inhibition of neutrophil degranulation in neutrophil-mediated tissue injury, it has been implicated in both neuroprotective and neurodegenerative effects, and it may also mediate both cell proliferation and cell death. Alternative splicing results in multiple transcript variants. This gene shares its 5' terminal exon with some transcripts from overlapping GeneID:57413, which encodes an immunoglobulin domain-containing protein. [provided by RefSeq, Nov 2014]

ADORA3 links:

TMIGD3 (HGNC:51375): (transmembrane and immunoglobulin domain containing 3) This gene encodes a transmembrane and immunoglobulin domain-containing protein. Alternative splicing results in multiple transcript variants, one of which shares its 5' terminal exon with that of the overlapping adenosine A3 receptor gene (GeneID:140), thus resulting in a fusion product. [provided by RefSeq, Nov 2014]

TMIGD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.007766217).

BP6

Variant 1-111500324-C-T is Benign according to our data. Variant chr1-111500324-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3035442.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADORA3	NM_000677.4 link	c.583G>A	p.Ala195Thr	missense_variant	Exon 2 of 2	ENST00000241356.5	NP_000668.1	P0DMS8-1
TMIGD3	NM_020683.7 link	c.350+2681G>A		intron_variant	Intron 1 of 5	ENST00000369716.9	NP_065734.5	P0DMS9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADORA3	ENST00000241356.5 link	c.583G>A	p.Ala195Thr	missense_variant	Exon 2 of 2	1	NM_000677.4	ENSP00000241356.4		P0DMS8-1
TMIGD3	ENST00000369716.9 link	c.350+2681G>A		intron_variant	Intron 1 of 5	1	NM_020683.7	ENSP00000358730.4		P0DMS9-2

Frequencies

GnomAD3 genomes

AF:

0.00129

AC:

197

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00442

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000406

AC:

102

AN:

251366

Hom.:

AF XY:

0.000309

AC XY:

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.00498

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000225

AC:

329

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000209

AC XY:

152

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00406

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000142

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.00129

AC:

197

AN:

152272

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00441

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000375

Hom.:

Bravo

AF:

0.00155

ESP6500AA

AF:

0.00545

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000461

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ADORA3-related disorder

Benign:1

May 22, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.21

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.76

M_CAP

Benign

0.0063

MetaRNN

Benign

0.0078

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.79

PROVEAN

Benign

-1.8

REVEL

Benign

0.073

Sift

Benign

0.056

Sift4G

Benign

0.065

Vest4

0.13

MVP

0.061

ClinPred

0.018

GERP RS

2.1

Varity_R

0.051

gMVP

0.16

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

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