6-132570626-G-A

Position:

• chr6-132570626-G-A

Variant summary

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

The NM_175067.1(TAAR6):​c.305G>A​(p.Arg102Lys) 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. 16/21 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)
• Consequence: TAAR6 NM_175067.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.367

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=0.07225698).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAAR6	NM_175067.1	c.305G>A	p.Arg102Lys	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.305G>A	p.Arg102Lys	missense_variant	1/1	6	NM_175067.1	ENSP00000275198.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Dec 03, 2024

The c.305G>A (p.R102K) 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 305, causing the arginine (R) at amino acid position 102 to be replaced by a lysine (K). 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	0.090
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.017
DANN	Benign	0.80
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.10	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.86	L
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.16
Sift	Benign	0.035	D
Sift4G	Benign	0.14	T
Polyphen		0.0020	B
Vest4		0.075
MutPred		0.51		Gain of methylation at R102 (P = 0.0124);
MVP		0.061
MPC		0.0095
ClinPred		0.14	T
GERP RS		-10
Varity_R		0.059
gMVP		0.079

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr6-132891765; COSMIC: COSV99256495;