chr6-132645723-A-T

Variant names:

• chr6-132645723-A-T
• rs574395819
• NM_138327.4:c.281T>A

Variant summary

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

The NM_138327.4(TAAR1):​c.281T>A​(p.Val94Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAAR1 NM_138327.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11

Genes affected

TAAR1 (HGNC:17734): (trace amine associated receptor 1) The protein encoded by this gene is a G-protein coupled receptor activated by trace amines. The encoded protein responds little or not at all to dopamine, serotonin, epinephrine, or histamine, but responds well to beta-phenylethylamine, p-tyramine, octopamine, and tryptamine. While primarily functioning in neurologic systems, there is evidence that this gene is involved in blood cell and immunologic functions as well. This gene is thought to be intronless. [provided by RefSeq, Nov 2015]

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 rank	MANE	Protein	UniProt
TAAR1	NM_138327.4	c.281T>A	p.Val94Asp	missense_variant	Exon 2 of 2	ENST00000275216.3	NP_612200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAAR1	ENST00000275216.3	c.281T>A	p.Val94Asp	missense_variant	Exon 2 of 2	6	NM_138327.4	ENSP00000275216.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.45
Sift	Benign	0.17	T
Sift4G	Benign	0.27	T
Polyphen		0.86	P
Vest4		0.58
MutPred		0.50		Gain of catalytic residue at V94 (P = 0.1859);
MVP		0.82
MPC		0.020
ClinPred		0.72	D
GERP RS		4.8
Varity_R		0.57
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs574395819; hg19: chr6-132966862;