6-132538903-T-C

Position:

• chr6-132538903-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_175057.4(TAAR9):​c.614T>C​(p.Leu205Pro) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAAR9 NM_175057.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.250

Genes affected

TAAR9 (HGNC:20977): (trace amine associated receptor 9) TAAR9 is a member of a large family of rhodopsin G protein-coupled receptors (GPCRs, or GPRs). GPCRs contain 7 transmembrane domains and transduce extracellular signals through heterotrimeric G proteins.[supplied by OMIM, Jul 2005]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.769

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAAR9	NM_175057.4	c.614T>C	p.Leu205Pro	missense_variant	1/1	ENST00000434551.3	NP_778227.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAAR9	ENST00000434551.3	c.614T>C	p.Leu205Pro	missense_variant	1/1	6	NM_175057.4	ENSP00000424607.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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

Feb 28, 2024

The c.614T>C (p.L205P) alteration is located in exon 1 (coding exon 1) of the TAAR9 gene. This alteration results from a T to C substitution at nucleotide position 614, causing the leucine (L) at amino acid position 205 to be replaced by a proline (P). 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	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.78	T
MetaRNN	Pathogenic	0.77	D
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.46	T
Sift4G	Benign	0.067	T
Polyphen		0.18	B
Vest4		0.81
MVP		0.54
GERP RS		5.3
Varity_R		0.63
gMVP		0.57

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: chr6-132860042;