Genetic Variant NM_175067.1:c.296A>G (chr6-132570617-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_175067.1(TAAR6):c.296A>G(p.Tyr99Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00472 in 1,613,756 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 27 hom. )

Consequence

TAAR6
NM_175067.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.48

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012710452).

BP6

Variant 6-132570617-A-G is Benign according to our data. Variant chr6-132570617-A-G is described in ClinVar as [Benign]. Clinvar id is 774647.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAAR6	NM_175067.1 link	c.296A>G	p.Tyr99Cys	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.296A>G	p.Tyr99Cys	missense_variant	Exon 1 of 1	6	NM_175067.1	ENSP00000275198.1		Q96RI8

Frequencies

GnomAD3 genomes

AF:

0.00345

AC:

523

AN:

151776

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00160

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00427

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000627

Gnomad FIN

AF:

0.000663

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00550

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.00351

AC:

881

AN:

251226

Hom.:

AF XY:

0.00343

AC XY:

465

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00370

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000882

Gnomad FIN exome

AF:

0.000831

Gnomad NFE exome

AF:

0.00579

Gnomad OTH exome

AF:

0.00408

GnomAD4 exome

AF:

0.00485

AC:

7095

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00477

AC XY:

3469

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00362

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000858

Gnomad4 FIN exome

AF:

0.00114

Gnomad4 NFE exome

AF:

0.00588

Gnomad4 OTH exome

AF:

0.00354

GnomAD4 genome

AF:

0.00344

AC:

523

AN:

151894

Hom.:

Cov.:

AF XY:

0.00295

AC XY:

219

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.00426

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000628

Gnomad4 FIN

AF:

0.000663

Gnomad4 NFE

AF:

0.00550

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00542

Hom.:

Bravo

AF:

0.00395

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00535

AC:

ExAC

AF:

0.00368

AC:

447

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00524

EpiControl

AF:

0.00468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 30, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.019

MetaRNN

Benign

0.013

MetaSVM

Uncertain

-0.054

MutationAssessor

Pathogenic

3.4

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-8.9

REVEL

Benign

0.26

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.36

MVP

0.23

MPC

0.059

ClinPred

0.072

GERP RS

5.0

Varity_R

0.93

gMVP

0.041

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