6-132588998-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003967.3(TAAR5):c.689C>T(p.Ala230Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TAAR5 NM_003967.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60

Genes affected

TAAR5 (HGNC:30236): (trace amine associated receptor 5) Enables trimethylamine receptor activity. Predicted to be involved in signal transduction. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2640645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAAR5	NM_003967.3	c.689C>T	p.Ala230Val	missense_variant	1/1	ENST00000258034.4
TAAR5	NM_001389527.1	c.689C>T	p.Ala230Val	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAAR5	ENST00000258034.4	c.689C>T	p.Ala230Val	missense_variant	1/1		NM_003967.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250372 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135404

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461778 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727182

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

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

Dec 17, 2021

The c.689C>T (p.A230V) alteration is located in exon 1 (coding exon 1) of the TAAR5 gene. This alteration results from a C to T substitution at nucleotide position 689, causing the alanine (A) at amino acid position 230 to be replaced by a valine (V). 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	0.21
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.057	T
Eigen	Benign	0.095
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	0.98	D
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.094
Sift	Uncertain	0.012	D
Sift4G	Benign	0.061	T
Polyphen		0.63	P
Vest4		0.29
MutPred		0.70		Loss of disorder (P = 0.0725);
MVP		0.50
MPC		0.016
ClinPred		0.89	D
GERP RS		3.8
Varity_R		0.39
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs745969010; hg19: chr6-132910137;