chr6-132570839-A-G

Position:

• chr6-132570839-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0067 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00070 (8 hom.)
• Consequence: TAAR6 NM_175067.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAAR6	NM_175067.1	c.518A>G	p.Tyr173Cys	missense_variant	1/1	ENST00000275198.1	NP_778237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAAR6	ENST00000275198.1	c.518A>G	p.Tyr173Cys	missense_variant	1/1	6	NM_175067.1	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

GnomAD3 exomes AF: 0.00170 AC: 427 AN: 250976 Hom.: 1 AF XY: 0.00121 AC XY: 164 AN XY: 135602

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 SAS exome AF: 0.0000327

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

Gnomad4 AFR exome AF: 0.0224

Gnomad4 AMR exome AF: 0.00208

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000369

Gnomad4 OTH exome AF: 0.00192

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

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.00536

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00100 Hom.: 1

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 v4.3

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
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

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

LitVar

Other links and lift over

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