6-132571148-T-C

Position:

• chr6-132571148-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_175067.1(TAAR6):​c.827T>C​(p.Ile276Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000109 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: TAAR6 NM_175067.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.00

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAAR6	NM_175067.1	c.827T>C	p.Ile276Thr	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.827T>C	p.Ile276Thr	missense_variant	1/1		NM_175067.1	ENSP00000275198	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461778 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 727194

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

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

May 31, 2023

The c.827T>C (p.I276T) alteration is located in exon 1 (coding exon 1) of the TAAR6 gene. This alteration results from a T to C substitution at nucleotide position 827, causing the isoleucine (I) at amino acid position 276 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	0.12
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.083	T
Eigen	Benign	0.061
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.11	B
Vest4		0.48
MutPred		0.73		Loss of stability (P = 0.0031);
MVP		0.75
MPC		0.017
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.45
gMVP		0.041

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-132892287;