Genetic Variant NM_175067.1:c.518A>G (chr6-132570839-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_175067.1(TAAR6):c.518A>G(p.Tyr173Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,614,134 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.0067 ( 12 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 8 hom. )

Consequence

TAAR6
NM_175067.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.170

Publications

7 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=0.0043700635).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0067 (1020/152276) while in subpopulation AFR AF = 0.0221 (917/41562). AF 95% confidence interval is 0.0209. There are 12 homozygotes in GnomAd4. There are 486 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAAR6	NM_175067.1 link	c.518A>G	p.Tyr173Cys	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.518A>G	p.Tyr173Cys	missense_variant	Exon 1 of 1	6	NM_175067.1	ENSP00000275198.1		Q96RI8

Frequencies

GnomAD3 genomes

AF:

0.00669

AC:

1018

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0221

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.00170

AC:

427

AN:

250976

AF XY:

0.00121

show subpopulations

Gnomad AFR exome

AF:

0.0229

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000530

Gnomad OTH exome

AF:

0.000818

GnomAD4 exome

AF:

0.000697

AC:

1019

AN:

1461858

Hom.:

Cov.:

AF XY:

0.000583

AC XY:

424

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.0224

AC:

750

AN:

33476

American (AMR)

AF:

0.00208

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00225

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000369

AC:

AN:

1111984

Other (OTH)

AF:

0.00192

AC:

116

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

144

216

288

360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00670

AC:

1020

AN:

152276

Hom.:

Cov.:

AF XY:

0.00653

AC XY:

486

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0221

AC:

917

AN:

41562

American (AMR)

AF:

0.00536

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68016

Other (OTH)

AF:

0.00520

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

105

157

210

262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00214

Hom.:

Bravo

AF:

0.00808

ESP6500AA

AF:

0.0204

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00206

AC:

250

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.21

MetaRNN

Benign

0.0044

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.3

PhyloP100

-0.17

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.1

REVEL

Benign

0.18

Sift

Uncertain

0.015

Sift4G

Uncertain

0.028

Polyphen

0.95

Vest4

0.12

MVP

0.75

MPC

0.0094

ClinPred

0.036

GERP RS

4.0

Varity_R

0.14

gMVP

0.13

Mutation Taster

=100/0

polymorphism

(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