Genetic Variant NM_003967.3:c.989G>C (chr6-132588698-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_003967.3(TAAR5):c.989G>C(p.Arg330Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R330C) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TAAR5
NM_003967.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.362

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050460517).

BP6

Variant 6-132588698-C-G is Benign according to our data. Variant chr6-132588698-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2606049.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003967.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAAR5	NM_003967.3	MANE Select	c.989G>C	p.Arg330Pro	missense	Exon 1 of 1	NP_003958.2	O14804
	TAAR5	NM_001389527.1		c.989G>C	p.Arg330Pro	missense	Exon 4 of 4	NP_001376456.1	O14804

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAAR5	ENST00000258034.4	TSL:6 MANE Select	c.989G>C	p.Arg330Pro	missense	Exon 1 of 1	ENSP00000258034.2	O14804

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460916

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726672

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26048

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86048

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111520

Other (OTH)

AF:

0.00

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.0082

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.54

M_CAP

Benign

0.010

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

0.36

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.68

REVEL

Benign

0.074

Sift

Benign

0.091

Sift4G

Benign

0.12

Polyphen

0.0

Vest4

0.072

MutPred

0.41

Gain of glycosylation at T331 (P = 0.0209)

MVP

0.47

MPC

0.012

ClinPred

0.083

GERP RS

2.6

Varity_R

0.13

gMVP

0.53

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over