6-132570814-G-A

Variant names:

• chr6-132570814-G-A
• rs17061401
• NM_175067.1:c.493G>A

Variant summary

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

The NM_175067.1(TAAR6):​c.493G>A​(p.Gly165Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,613,974 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.011 (25 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (19 hom.)
• Consequence: TAAR6 NM_175067.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442

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=0.002559185).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1620/152148) while in subpopulation AFR AF= 0.0349 (1450/41498). AF 95% confidence interval is 0.0334. There are 25 homozygotes in gnomad4. There are 746 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAAR6	NM_175067.1	c.493G>A	p.Gly165Ser	missense_variant	Exon 1 of 1	ENST00000275198.1	NP_778237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAAR6	ENST00000275198.1	c.493G>A	p.Gly165Ser	missense_variant	Exon 1 of 1	6	NM_175067.1	ENSP00000275198.1

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1613 AN: 152030 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00773

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00908

GnomAD3 exomes AF: 0.00291 AC: 730 AN: 250914 Hom.: 7 AF XY: 0.00208 AC XY: 282 AN XY: 135558

Gnomad AFR exome AF: 0.0373

Gnomad AMR exome AF: 0.00234

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00124 AC: 1813 AN: 1461826 Hom.: 19 Cov.: 31 AF XY: 0.00110 AC XY: 798 AN XY: 727224

Gnomad4 AFR exome AF: 0.0353

Gnomad4 AMR exome AF: 0.00275

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000277

Gnomad4 OTH exome AF: 0.00290

GnomAD4 genome AF: 0.0106 AC: 1620 AN: 152148 Hom.: 25 Cov.: 32 AF XY: 0.0100 AC XY: 746 AN XY: 74386

Gnomad4 AFR AF: 0.0349

Gnomad4 AMR AF: 0.00766

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.00993

Alfa AF: 0.00255 Hom.: 7

Bravo AF: 0.0123

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0368 AC: 162

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00348 AC: 423

Asia WGS AF: 0.00982 AC: 34 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.1
DANN	Benign	0.57
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.075	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.032
Sift	Benign	0.29	T
Sift4G	Benign	0.13	T
Polyphen		0.0080	B
Vest4		0.082
MVP		0.45
MPC		0.010
ClinPred		0.0058	T
GERP RS		2.4
Varity_R		0.049
gMVP		0.11

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: rs17061401; hg19: chr6-132891953; COSMIC: COSV51582517;