Genetic Variant TAAR6:p.Ala228Val (chr6-132571004-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_175067.1(TAAR6):c.683C>T(p.Ala228Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,613,718 control chromosomes in the GnomAD database, including 1,395 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.053 ( 732 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 663 hom. )

Consequence

TAAR6
NM_175067.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.13

Publications

9 publications found

Variant links:

Genes affected

TAAR6 (HGNC:20978): (trace amine associated receptor 6) This gene encodes a seven-transmembrane G-protein-coupled receptor that likely functions as a receptor for endogenous trace amines. Mutations in this gene may be associated with schizophrenia.[provided by RefSeq, Feb 2010]

TAAR6 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=0.0018667579).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAAR6	NM_175067.1 link	c.683C>T	p.Ala228Val	missense_variant	Exon 1 of 1	ENST00000275198.1	NP_778237.1	Q96RI8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAAR6	ENST00000275198.1 link	c.683C>T	p.Ala228Val	missense_variant	Exon 1 of 1	6	NM_175067.1	ENSP00000275198.1		Q96RI8

Frequencies

GnomAD3 genomes

AF:

0.0534

AC:

8109

AN:

151864

Hom.:

733

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0237

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00138

Gnomad OTH

AF:

0.0464

GnomAD2 exomes

AF:

0.0147

AC:

3683

AN:

250638

AF XY:

0.0108

show subpopulations

Gnomad AFR exome

AF:

0.183

Gnomad AMR exome

AF:

0.0134

Gnomad ASJ exome

AF:

0.00368

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00124

Gnomad OTH exome

AF:

0.00999

GnomAD4 exome

AF:

0.00615

AC:

8987

AN:

1461736

Hom.:

663

Cov.:

AF XY:

0.00544

AC XY:

3955

AN XY:

727170

show subpopulations

African (AFR)

AF:

0.185

AC:

6191

AN:

33476

American (AMR)

AF:

0.0147

AC:

656

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00306

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39654

South Asian (SAS)

AF:

0.000313

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00972

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00103

AC:

1147

AN:

1111956

Other (OTH)

AF:

0.0137

AC:

826

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

440

880

1319

1759

2199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

208

416

624

832

1040

<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:

0.0535

AC:

8131

AN:

151982

Hom.:

732

Cov.:

AF XY:

0.0516

AC XY:

3828

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.182

AC:

7547

AN:

41410

American (AMR)

AF:

0.0236

AC:

361

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000208

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10548

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00138

AC:

AN:

67982

Other (OTH)

AF:

0.0478

AC:

101

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

338

676

1015

1353

1691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<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:

0.0191

Hom.:

618

Bravo

AF:

0.0602

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.172

AC:

759

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.0174

AC:

2113

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.00196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

Eigen

Benign

-0.0042

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.4

PhyloP100

2.1

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.091

Sift

Uncertain

0.010

Sift4G

Uncertain

0.013

Polyphen

0.99

Vest4

0.12

MPC

0.047

ClinPred

0.024

GERP RS

4.2

Varity_R

0.40

gMVP

0.082

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over