chr6-132571117-G-A

Position:

• chr6-132571117-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_175067.1(TAAR6):​c.796G>A​(p.Ala266Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TAAR6 NM_175067.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26946133).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAAR6	NM_175067.1	c.796G>A	p.Ala266Thr	missense_variant	1/1	ENST00000275198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAAR6	ENST00000275198.1	c.796G>A	p.Ala266Thr	missense_variant	1/1		NM_175067.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461758 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727184

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.796G>A (p.A266T) alteration is located in exon 1 (coding exon 1) of the TAAR6 gene. This alteration results from a G to A substitution at nucleotide position 796, causing the alanine (A) at amino acid position 266 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	0.86	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.15
Sift	Benign	0.039	D
Sift4G	Benign	0.082	T
Polyphen		0.014	B
Vest4		0.12
MutPred		0.71		Gain of sheet (P = 0.0827);
MVP		0.41
MPC		0.015
ClinPred		0.37	T
GERP RS		4.2
Varity_R		0.12
gMVP		0.040

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1776639834; hg19: chr6-132892256;