rs2800889

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000677.4(ADORA3):c.797T>A(p.Met266Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0184 in 1,614,210 control chromosomes in the GnomAD database, including 378 homozygotes. 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: 𝑓 0.019 ( 29 hom., cov: 32)

Exomes 𝑓: 0.018 ( 349 hom. )

Consequence

ADORA3
NM_000677.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.84

Publications

14 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060951114).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0194 (2959/152334) while in subpopulation AFR AF = 0.0267 (1110/41572). AF 95% confidence interval is 0.0254. There are 29 homozygotes in GnomAd4. There are 1365 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADORA3	NM_000677.4 link	c.797T>A	p.Met266Lys	missense_variant	Exon 2 of 2	ENST00000241356.5	NP_000668.1	P0DMS8-1
TMIGD3	NM_020683.7 link	c.350+2895T>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.797T>A	p.Met266Lys	missense_variant	Exon 2 of 2	1	NM_000677.4	ENSP00000241356.4		P0DMS8-1
TMIGD3	ENST00000369716.9 link	c.350+2895T>A		intron_variant	Intron 1 of 5	1	NM_020683.7	ENSP00000358730.4		P0DMS9-2

Frequencies

GnomAD3 genomes

AF:

0.0194

AC:

2958

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0267

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.0100

Gnomad SAS

AF:

0.0228

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0194

Gnomad OTH

AF:

0.0258

GnomAD2 exomes

AF:

0.0172

AC:

4331

AN:

251436

AF XY:

0.0178

show subpopulations

Gnomad AFR exome

AF:

0.0277

Gnomad AMR exome

AF:

0.0111

Gnomad ASJ exome

AF:

0.0156

Gnomad EAS exome

AF:

0.00555

Gnomad FIN exome

AF:

0.00286

Gnomad NFE exome

AF:

0.0194

Gnomad OTH exome

AF:

0.0171

GnomAD4 exome

AF:

0.0183

AC:

26773

AN:

1461876

Hom.:

349

Cov.:

AF XY:

0.0186

AC XY:

13515

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0269

AC:

901

AN:

33480

American (AMR)

AF:

0.0118

AC:

528

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

369

AN:

26136

East Asian (EAS)

AF:

0.0149

AC:

591

AN:

39696

South Asian (SAS)

AF:

0.0261

AC:

2255

AN:

86256

European-Finnish (FIN)

AF:

0.00281

AC:

150

AN:

53420

Middle Eastern (MID)

AF:

0.0366

AC:

211

AN:

5768

European-Non Finnish (NFE)

AF:

0.0186

AC:

20661

AN:

1112002

Other (OTH)

AF:

0.0183

AC:

1107

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1861

3721

5582

7442

9303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

766

1532

2298

3064

3830

<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

AF:

0.0194

AC:

2959

AN:

152334

Hom.:

Cov.:

AF XY:

0.0183

AC XY:

1365

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0267

AC:

1110

AN:

41572

American (AMR)

AF:

0.0143

AC:

219

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

AN:

3470

East Asian (EAS)

AF:

0.0102

AC:

AN:

5186

South Asian (SAS)

AF:

0.0224

AC:

108

AN:

4828

European-Finnish (FIN)

AF:

0.00198

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0194

AC:

1319

AN:

68036

Other (OTH)

AF:

0.0255

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

150

301

451

602

752

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0188

Hom.:

Bravo

AF:

0.0208

TwinsUK

AF:

0.0197

AC:

ALSPAC

AF:

0.0234

AC:

ESP6500AA

AF:

0.0238

AC:

105

ESP6500EA

AF:

0.0188

AC:

162

ExAC

AF:

0.0178

AC:

2160

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0233

EpiControl

AF:

0.0233

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Uncertain

0.51

Eigen

Benign

-0.17

Eigen_PC

Benign

0.025

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0061

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

5.8

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.13

Sift

Uncertain

0.013

Sift4G

Uncertain

0.037

Vest4

0.19

ClinPred

0.020

GERP RS

5.4

Varity_R

0.60

gMVP

0.60

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over