chr4-103719165-C-T

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

3
12
4

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

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
TACR3NM_001059.3 linkc.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
TACR3ENST00000304883.3 linkc.511G>A p.Ala171Thr missense_variant Exon 1 of 5 1 NM_001059.3 ENSP00000303325.2 P29371

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461886
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727244
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.000176
AC:
7
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1112008
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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.:
32

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
D
BayesDel_noAF
Pathogenic
0.22
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.56
D
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.91
D
M_CAP
Uncertain
0.095
D
MetaRNN
Uncertain
0.66
D
MetaSVM
Uncertain
-0.27
T
MutationAssessor
Uncertain
2.3
M
PhyloP100
3.6
PrimateAI
Pathogenic
0.82
D
PROVEAN
Uncertain
-2.7
D
REVEL
Uncertain
0.63
Sift
Benign
0.031
D
Sift4G
Benign
0.10
T
Polyphen
0.99
D
Vest4
0.35
MutPred
0.72
Loss of glycosylation at S172 (P = 0.0362);
MVP
0.95
MPC
1.0
ClinPred
0.99
D
GERP RS
5.1
Varity_R
0.57
gMVP
0.82
Mutation Taster
=54/46
polymorphism

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

Other links and lift over

dbSNP: rs201195175; hg19: chr4-104640322; COSMIC: COSV59199643; API