rs17061404

Variant names:

• chr6-132570839-A-G
• rs17061404
• NM_175067.1:c.518A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000275198.1(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 ENST00000275198.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• Publications: 7 publications found

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]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000275198.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAAR6	NM_175067.1	MANE Select	c.518A>G	p.Tyr173Cys	missense	Exon 1 of 1	NP_778237.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAAR6	ENST00000275198.1	TSL:6 MANE Select	c.518A>G	p.Tyr173Cys	missense	Exon 1 of 1	ENSP00000275198.1

Frequencies

GnomAD3 genomes AF: 0.00669 AC: 1018 AN: 152158 Hom.: 12 Cov.: 32

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

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.: 8 Cov.: 31 AF XY: 0.000583 AC XY: 424 AN XY: 727238

African (AFR) AF: 0.0224 AC: 750 AN: 33476

American (AMR) AF: 0.00208 AC: 93 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5766

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1111984

Other (OTH) AF: 0.00192 AC: 116 AN: 60396

GnomAD4 genome AF: 0.00670 AC: 1020 AN: 152276 Hom.: 12 Cov.: 32 AF XY: 0.00653 AC XY: 486 AN XY: 74460

African (AFR) AF: 0.0221 AC: 917 AN: 41562

American (AMR) AF: 0.00536 AC: 82 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68016

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00214 Hom.: 6

Bravo AF: 0.00808

ESP6500AA AF: 0.0204 AC: 90

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00206 AC: 250

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.17
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.18
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.028	D
Polyphen		0.95	P
Vest4		0.12
MVP		0.75
MPC		0.0094
ClinPred		0.036	T
GERP RS		4.0
Varity_R		0.14
gMVP		0.13
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs17061404; hg19: chr6-132891978; COSMIC: COSV51583400;