Variant 6-132588911-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003967.3(TAAR5):c.776G>T(p.Gly259Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,848 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: 0.0000062 ( 0 hom. )

Consequence

TAAR5
NM_003967.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.609

Variant links:

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]

TAAR5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18919772).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAAR5	NM_003967.3 linkuse as main transcript	c.776G>T	p.Gly259Val	missense_variant	1/1	ENST00000258034.4	NP_003958.2	O14804
TAAR5	NM_001389527.1 linkuse as main transcript	c.776G>T	p.Gly259Val	missense_variant	4/4		NP_001376456.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAAR5	ENST00000258034.4 linkuse as main transcript	c.776G>T	p.Gly259Val	missense_variant	1/1	6	NM_003967.3	ENSP00000258034.2		O14804

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250978

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2022

The c.776G>T (p.G259V) alteration is located in exon 1 (coding exon 1) of the TAAR5 gene. This alteration results from a G to T substitution at nucleotide position 776, causing the glycine (G) at amino acid position 259 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

0.19

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.070

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.37

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0089

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.4

REVEL

Benign

0.20

Sift

Benign

0.54

Sift4G

Benign

0.48

Polyphen

0.24

Vest4

0.38

MutPred

0.60

Gain of helix (P = 0.2294);

MVP

0.47

MPC

0.079

ClinPred

0.40

GERP RS

3.7

Varity_R

0.36

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over