6-132571114-G-A

Position:

• chr6-132571114-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.793G>A​(p.Val265Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.079 in 1,613,938 control chromosomes in the GnomAD database, including 5,547 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 0.076 (503 hom., cov: 32)
  • Exomes 𝑓: 0.079 (5044 hom.)
• Consequence: TAAR6 NM_175067.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.832

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=0.0027578175).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAAR6	NM_175067.1	c.793G>A	p.Val265Ile	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.793G>A	p.Val265Ile	missense_variant	1/1		NM_175067.1	ENSP00000275198	P1

Frequencies

GnomAD3 genomes AF: 0.0757 AC: 11506 AN: 152060 Hom.: 503 Cov.: 32

Gnomad AFR AF: 0.0605

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.0742

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0880

Gnomad OTH AF: 0.0664

GnomAD3 exomes AF: 0.0730 AC: 18311 AN: 250952 Hom.: 805 AF XY: 0.0757 AC XY: 10267 AN XY: 135630

Gnomad AFR exome AF: 0.0616

Gnomad AMR exome AF: 0.0373

Gnomad ASJ exome AF: 0.0465

Gnomad EAS exome AF: 0.0105

Gnomad SAS exome AF: 0.0817

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.0872

Gnomad OTH exome AF: 0.0848

GnomAD4 exome AF: 0.0794 AC: 116034 AN: 1461760 Hom.: 5044 Cov.: 32 AF XY: 0.0801 AC XY: 58226 AN XY: 727186

Gnomad4 AFR exome AF: 0.0600

Gnomad4 AMR exome AF: 0.0397

Gnomad4 ASJ exome AF: 0.0432

Gnomad4 EAS exome AF: 0.0147

Gnomad4 SAS exome AF: 0.0824

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.0828

Gnomad4 OTH exome AF: 0.0760

GnomAD4 genome AF: 0.0756 AC: 11507 AN: 152178 Hom.: 503 Cov.: 32 AF XY: 0.0761 AC XY: 5665 AN XY: 74398

Gnomad4 AFR AF: 0.0603

Gnomad4 AMR AF: 0.0560

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.0739

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.0881

Gnomad4 OTH AF: 0.0681

Alfa AF: 0.0785 Hom.: 1230

Bravo AF: 0.0701

TwinsUK AF: 0.0766 AC: 284

ALSPAC AF: 0.0828 AC: 319

ESP6500AA AF: 0.0629 AC: 277

ESP6500EA AF: 0.0807 AC: 694

ExAC AF: 0.0759 AC: 9219

Asia WGS AF: 0.0410 AC: 143 AN: 3478

EpiCase AF: 0.0847

EpiControl AF: 0.0903

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.024
DANN	Benign	0.61
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.37	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.028
Sift	Benign	0.83	T
Sift4G	Benign	0.94	T
Polyphen		0.0	B
Vest4		0.014
MPC		0.0097
ClinPred		0.0022	T
GERP RS		-6.0
Varity_R		0.037
gMVP		0.018

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: rs8192624; hg19: chr6-132892253; COSMIC: COSV51583150;