rs8192625

Positions:

• chr6-132571193-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175067.1(TAAR6):​c.872G>A​(p.Cys291Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0693 in 1,613,852 control chromosomes in the GnomAD database, including 4,185 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.077 (467 hom., cov: 32)
  • Exomes 𝑓: 0.069 (3718 hom.)
• Consequence: TAAR6 NM_175067.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.554

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=0.0021861494).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAAR6	NM_175067.1	c.872G>A	p.Cys291Tyr	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.872G>A	p.Cys291Tyr	missense_variant	1/1		NM_175067.1	ENSP00000275198	P1

Frequencies

GnomAD3 genomes AF: 0.0766 AC: 11636 AN: 151984 Hom.: 467 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.0476

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.0631

Gnomad FIN AF: 0.0802

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0740

Gnomad OTH AF: 0.0657

GnomAD3 exomes AF: 0.0619 AC: 15536 AN: 250970 Hom.: 609 AF XY: 0.0629 AC XY: 8533 AN XY: 135630

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.0292

Gnomad ASJ exome AF: 0.0278

Gnomad EAS exome AF: 0.00925

Gnomad SAS exome AF: 0.0697

Gnomad FIN exome AF: 0.0790

Gnomad NFE exome AF: 0.0718

Gnomad OTH exome AF: 0.0652

GnomAD4 exome AF: 0.0686 AC: 100204 AN: 1461750 Hom.: 3718 Cov.: 32 AF XY: 0.0685 AC XY: 49791 AN XY: 727186

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.0305

Gnomad4 ASJ exome AF: 0.0246

Gnomad4 EAS exome AF: 0.0137

Gnomad4 SAS exome AF: 0.0693

Gnomad4 FIN exome AF: 0.0817

Gnomad4 NFE exome AF: 0.0714

Gnomad4 OTH exome AF: 0.0650

GnomAD4 genome AF: 0.0766 AC: 11645 AN: 152102 Hom.: 467 Cov.: 32 AF XY: 0.0754 AC XY: 5607 AN XY: 74348

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0476

Gnomad4 ASJ AF: 0.0280

Gnomad4 EAS AF: 0.0129

Gnomad4 SAS AF: 0.0623

Gnomad4 FIN AF: 0.0802

Gnomad4 NFE AF: 0.0740

Gnomad4 OTH AF: 0.0674

Alfa AF: 0.0702 Hom.: 756

Bravo AF: 0.0730

TwinsUK AF: 0.0701 AC: 260

ALSPAC AF: 0.0737 AC: 284

ESP6500AA AF: 0.103 AC: 456

ESP6500EA AF: 0.0677 AC: 582

ExAC AF: 0.0645 AC: 7831

Asia WGS AF: 0.0510 AC: 175 AN: 3478

EpiCase AF: 0.0677

EpiControl AF: 0.0677

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.53
DANN	Benign	0.18
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.9	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	3.3	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.020
MPC		0.0088
ClinPred		0.0021	T
GERP RS		3.9
Varity_R		0.049
gMVP		0.12

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

Other links and lift over

dbSNP: rs8192625; hg19: chr6-132892332; COSMIC: COSV51583366;