Genetic Variant TACR3:p.Ala171Thr (chr4-103719165-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM5

The NM_001059.3(TACR3):c.511G>A(p.Ala171Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A171P) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

TACR3
NM_001059.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.62

Publications

1 publications found

Variant links:

Genes affected

TACR3 (HGNC:11528): (tachykinin receptor 3) This gene belongs to a family of genes that function as receptors for tachykinins. Receptor affinities are specified by variations in the 5'-end of the sequence. The receptors belonging to this family are characterized by interactions with G proteins and 7 hydrophobic transmembrane regions. This gene encodes the receptor for the tachykinin neurokinin 3, also referred to as neurokinin B. [provided by RefSeq, Jul 2008]

TACR3 Gene-Disease associations (from GenCC):

hypogonadotropic hypogonadism 11 with or without anosmia
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
hypogonadotropic hypogonadism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TACR3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chr4-103719165-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 180148.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR3	NM_001059.3 link	c.511G>A	p.Ala171Thr	missense_variant	Exon 1 of 5	ENST00000304883.3	NP_001050.1	P29371

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR3	ENST00000304883.3 link	c.511G>A	p.Ala171Thr	missense_variant	Exon 1 of 5	1	NM_001059.3	ENSP00000303325.2		P29371

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.000176

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112008

Other (OTH)

AF:

0.0000166

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.095

MetaRNN

Uncertain

0.66

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.3

PhyloP100

3.6

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.7

REVEL

Uncertain

0.63

Sift

Benign

0.031

Sift4G

Benign

0.10

Polyphen

0.99

Vest4

0.35

MutPred

0.72

Loss of glycosylation at S172 (P = 0.0362);

MVP

0.95

MPC

1.0

ClinPred

0.99

GERP RS

5.1

Varity_R

0.57

gMVP

0.82

Mutation Taster

=54/46

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over