6-132645153-G-A

Variant names:

• chr6-132645153-G-A
• NM_138327.4:c.851C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138327.4(TAAR1):​c.851C>T​(p.Thr284Ile) 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. 15/21 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: TAAR1 NM_138327.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.858

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.064970255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAAR1	NM_138327.4	c.851C>T	p.Thr284Ile	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.851C>T	p.Thr284Ile	missense_variant	Exon 2 of 2	6	NM_138327.4	ENSP00000275216.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 09, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.851C>T (p.T284I) alteration is located in exon 1 (coding exon 1) of the TAAR1 gene. This alteration results from a C to T substitution at nucleotide position 851, causing the threonine (T) at amino acid position 284 to be replaced by an isoleucine (I). 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	0.079
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.1
DANN	Benign	0.31
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.59	N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.54	N
REVEL	Benign	0.035
Sift	Benign	0.39	T
Sift4G	Benign	0.39	T
Polyphen		0.0070	B
Vest4		0.066
MutPred		0.39		Loss of glycosylation at T284 (P = 0.0816);
MVP		0.29
MPC		0.010
ClinPred		0.051	T
GERP RS		0.13
Varity_R		0.023
gMVP		0.32

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-132966292;