Genetic Variant TAAR6:p.Cys186Tyr (chr6-132570878-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_175067.1(TAAR6):c.557G>A(p.Cys186Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00156 in 1,614,174 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C186R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00089 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 2 hom. )

Consequence

TAAR6
NM_175067.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.85

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04377234).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAAR6	NM_175067.1 link	c.557G>A	p.Cys186Tyr	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.557G>A	p.Cys186Tyr	missense_variant	Exon 1 of 1	6	NM_175067.1	ENSP00000275198.1		Q96RI8

Frequencies

GnomAD3 genomes

AF:

0.000887

AC:

135

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00146

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000956

AC:

240

AN:

251076

Hom.:

AF XY:

0.00106

AC XY:

144

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00177

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00163

AC:

2379

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1156

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00203

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.000886

AC:

135

AN:

152318

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00146

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00141

Hom.:

Bravo

AF:

0.000933

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.000881

AC:

107

EpiCase

AF:

0.00180

EpiControl

AF:

0.00184

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 31, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.557G>A (p.C186Y) alteration is located in exon 1 (coding exon 1) of the TAAR6 gene. This alteration results from a G to A substitution at nucleotide position 557, causing the cysteine (C) at amino acid position 186 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.083

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

M_CAP

Benign

0.031

MetaRNN

Benign

0.044

MetaSVM

Uncertain

-0.11

MutationAssessor

Pathogenic

3.2

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-9.8

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

0.99

Vest4

0.28

MVP

0.77

MPC

0.028

ClinPred

0.68

GERP RS

3.3

Varity_R

0.90

gMVP

0.13

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