6-132571343-T-C

Position:

• chr6-132571343-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_175067.1(TAAR6):​c.1022T>C​(p.Phe341Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,457,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000027 (0 hom.)
• Consequence: TAAR6 NM_175067.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.10

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14953831).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAAR6	NM_175067.1	c.1022T>C	p.Phe341Ser	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.1022T>C	p.Phe341Ser	missense_variant	1/1		NM_175067.1	ENSP00000275198	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1457426 Hom.: 0 Cov.: 32 AF XY: 0.00000414 AC XY: 3 AN XY: 725014

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: 0.0000117

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

Feb 06, 2023

The c.1022T>C (p.F341S) 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 1022, causing the phenylalanine (F) at amino acid position 341 to be replaced by a serine (S). 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	Uncertain	0.40
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.12
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.015	D
Polyphen		0.62	P
Vest4		0.20
MutPred		0.47		Gain of disorder (P = 0.0036);
MVP		0.23
MPC		0.013
ClinPred		0.81	D
GERP RS		2.8
Varity_R		0.34
gMVP		0.062

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: rs1776644346; hg19: chr6-132892482;