dbSNP rs8192627: TAAR8:p.Asp328Ala (chr6-132553675-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_053278.3(TAAR8):c.983A>C(p.Asp328Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0665 in 1,609,538 control chromosomes in the GnomAD database, including 3,983 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.056 ( 320 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3663 hom. )

Consequence

TAAR8
NM_053278.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.45

Publications

12 publications found

Variant links:

Genes affected

TAAR8 (HGNC:14964): (trace amine associated receptor 8) This gene is part of the trace amine receptor cluster on chromosome 6 and encodes an orphan G-protein coupled receptor. Upregulated expression of this gene in astroglial cells upon exposure to lipopolysaccharides suggests a function for the encoded protein in the brain. [provided by RefSeq, Jul 2016]

TAAR8 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=0.0019015968).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAAR8	NM_053278.3 link	c.983A>C	p.Asp328Ala	missense_variant	Exon 1 of 1	ENST00000275200.2	NP_444508.1	Q969N4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAAR8	ENST00000275200.2 link	c.983A>C	p.Asp328Ala	missense_variant	Exon 1 of 1	6	NM_053278.3	ENSP00000275200.1		Q969N4

Frequencies

GnomAD3 genomes

AF:

0.0564

AC:

8575

AN:

152136

Hom.:

318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0282

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.0377

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.0106

Gnomad SAS

AF:

0.0461

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0750

Gnomad OTH

AF:

0.0464

GnomAD2 exomes

AF:

0.0573

AC:

14186

AN:

247436

AF XY:

0.0587

show subpopulations

Gnomad AFR exome

AF:

0.0294

Gnomad AMR exome

AF:

0.0235

Gnomad ASJ exome

AF:

0.0213

Gnomad EAS exome

AF:

0.00790

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.0744

Gnomad OTH exome

AF:

0.0646

GnomAD4 exome

AF:

0.0676

AC:

98522

AN:

1457284

Hom.:

3663

Cov.:

AF XY:

0.0672

AC XY:

48722

AN XY:

724654

show subpopulations

African (AFR)

AF:

0.0286

AC:

953

AN:

33284

American (AMR)

AF:

0.0248

AC:

1094

AN:

44124

Ashkenazi Jewish (ASJ)

AF:

0.0204

AC:

531

AN:

26018

East Asian (EAS)

AF:

0.0101

AC:

400

AN:

39650

South Asian (SAS)

AF:

0.0454

AC:

3852

AN:

84936

European-Finnish (FIN)

AF:

0.116

AC:

6162

AN:

53040

Middle Eastern (MID)

AF:

0.0507

AC:

291

AN:

5742

European-Non Finnish (NFE)

AF:

0.0736

AC:

81702

AN:

1110268

Other (OTH)

AF:

0.0587

AC:

3537

AN:

60222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

4417

8834

13252

17669

22086

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2906

5812

8718

11624

14530

<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:

0.0564

AC:

8589

AN:

152254

Hom.:

320

Cov.:

AF XY:

0.0562

AC XY:

4186

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0283

AC:

1178

AN:

41558

American (AMR)

AF:

0.0377

AC:

577

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0173

AC:

AN:

3472

East Asian (EAS)

AF:

0.0106

AC:

AN:

5186

South Asian (SAS)

AF:

0.0460

AC:

222

AN:

4830

European-Finnish (FIN)

AF:

0.109

AC:

1156

AN:

10578

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0750

AC:

5104

AN:

68018

Other (OTH)

AF:

0.0487

AC:

103

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

413

826

1238

1651

2064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0647

Hom.:

1650

Bravo

AF:

0.0485

TwinsUK

AF:

0.0728

AC:

270

ALSPAC

AF:

0.0752

AC:

290

ESP6500AA

AF:

0.0272

AC:

120

ESP6500EA

AF:

0.0719

AC:

618

ExAC

AF:

0.0581

AC:

7054

Asia WGS

AF:

0.0300

AC:

103

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.5

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0045

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.28

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

1.4

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.30

REVEL

Benign

0.13

Sift

Uncertain

0.011

Sift4G

Benign

0.061

Polyphen

0.0020

Vest4

0.032

MPC

0.039

ClinPred

0.0071

GERP RS

0.63

Varity_R

0.078

gMVP

0.067

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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