6-132617673-A-C

Variant names:

• chr6-132617673-A-C
• rs141239990
• NM_001033080.1:c.533T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001033080.1(TAAR2):​c.533T>G​(p.Val178Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V178E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TAAR2 NM_001033080.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.34
• Publications: 0 publications found

Genes affected

TAAR2 (HGNC:4514): (trace amine associated receptor 2) Predicted to enable trace-amine receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000290584 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033080.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAAR2	NM_001033080.1	MANE Select	c.533T>G	p.Val178Gly	missense	Exon 2 of 2	NP_001028252.1	Q9P1P5-1
	TAAR2	NM_014626.3		c.398T>G	p.Val133Gly	missense	Exon 1 of 1	NP_055441.2	Q9P1P5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAAR2	ENST00000367931.1	TSL:1 MANE Select	c.533T>G	p.Val178Gly	missense	Exon 2 of 2	ENSP00000356908.1	Q9P1P5-1
	TAAR2	ENST00000275191.2	TSL:6	c.398T>G	p.Val133Gly	missense	Exon 1 of 1	ENSP00000275191.2	Q9P1P5-2
	ENSG00000290584	ENST00000466706.2	TSL:6	n.171-928T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461646 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727134

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111960

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.3
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.47
MutPred		0.53		Loss of stability (P = 0.0036)
MVP		0.64
MPC		0.032
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.81
gMVP		0.44
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs141239990; hg19: chr6-132938812;