chr6-132571004-C-T

Position:

• chr6-132571004-C-T

Variant summary

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

The NM_175067.1(TAAR6):​c.683C>T​(p.Ala228Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,613,718 control chromosomes in the GnomAD database, including 1,395 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.053 (732 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (663 hom.)
• Consequence: TAAR6 NM_175067.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13

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=0.0018667579).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAAR6	NM_175067.1	c.683C>T	p.Ala228Val	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.683C>T	p.Ala228Val	missense_variant	1/1	6	NM_175067.1	ENSP00000275198.1

Frequencies

GnomAD3 genomes AF: 0.0534 AC: 8109 AN: 151864 Hom.: 733 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0237

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00138

Gnomad OTH AF: 0.0464

GnomAD3 exomes AF: 0.0147 AC: 3683 AN: 250638 Hom.: 296 AF XY: 0.0108 AC XY: 1468 AN XY: 135462

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.0134

Gnomad ASJ exome AF: 0.00368

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00124

Gnomad OTH exome AF: 0.00999

GnomAD4 exome AF: 0.00615 AC: 8987 AN: 1461736 Hom.: 663 Cov.: 31 AF XY: 0.00544 AC XY: 3955 AN XY: 727170

Gnomad4 AFR exome AF: 0.185

Gnomad4 AMR exome AF: 0.0147

Gnomad4 ASJ exome AF: 0.00306

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.000313

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00103

Gnomad4 OTH exome AF: 0.0137

GnomAD4 genome AF: 0.0535 AC: 8131 AN: 151982 Hom.: 732 Cov.: 32 AF XY: 0.0516 AC XY: 3828 AN XY: 74250

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.0236

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00138

Gnomad4 OTH AF: 0.0478

Alfa AF: 0.0115 Hom.: 230

Bravo AF: 0.0602

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.172 AC: 759

ESP6500EA AF: 0.00186 AC: 16

ExAC AF: 0.0174 AC: 2113

Asia WGS AF: 0.0210 AC: 74 AN: 3478

EpiCase AF: 0.00136

EpiControl AF: 0.00196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.083	T
Eigen	Benign	-0.0042
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.091
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.013	D
Polyphen		0.99	D
Vest4		0.12
MPC		0.047
ClinPred		0.024	T
GERP RS		4.2
Varity_R		0.40
gMVP		0.082

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: rs17061409; hg19: chr6-132892143; COSMIC: COSV51584086;