rs376107701

Variant names:

• chr6-132617490-T-A
• rs376107701
• NM_001033080.1:c.716A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-132617490-T-A
• chr6-132617490-T-C
• chr6-132617490-T-G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001033080.1(TAAR2):​c.716A>T​(p.His239Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. H239R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAAR2 NM_001033080.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.93
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.941

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.716A>T	p.His239Leu	missense	Exon 2 of 2	NP_001028252.1	Q9P1P5-1
	TAAR2	NM_014626.3		c.581A>T	p.His194Leu	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.716A>T	p.His239Leu	missense	Exon 2 of 2	ENSP00000356908.1	Q9P1P5-1
	TAAR2	ENST00000275191.2	TSL:6	c.581A>T	p.His194Leu	missense	Exon 1 of 1	ENSP00000275191.2	Q9P1P5-2
	ENSG00000290584	ENST00000466706.2	TSL:6	n.171-745A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.065	T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.9
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.77		Loss of disorder (P = 0.0349)
MVP		0.79
MPC		0.033
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.54
gMVP		0.68
Mutation Taster		=57/43	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: rs376107701; hg19: chr6-132938629;