4-103719165-C-A

Variant summary

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

The NM_001059.3(TACR3):​c.511G>T​(p.Ala171Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,614,018 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: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

TACR3
NM_001059.3 missense

Scores

1
11
7

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>T p.Ala171Ser 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>T p.Ala171Ser missense_variant Exon 1 of 5 1 NM_001059.3 ENSP00000303325.2 P29371

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152132
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251462
AF XY:
0.00
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000109
AC:
16
AN:
1461886
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
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:
0.0000252
AC:
1
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:
0.0000135
AC:
15
AN:
1112008
Other (OTH)
AF:
0.00
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.491
Heterozygous variant carriers
0
1
2
4
5
6
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
AF:
0.00000657
AC:
1
AN:
152132
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74306
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41438
American (AMR)
AF:
0.00
AC:
0
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5194
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10600
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68034
Other (OTH)
AF:
0.00
AC:
0
AN:
2086
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.675
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Uncertain
0.16
D
BayesDel_noAF
Uncertain
-0.010
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.30
T
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.87
D
M_CAP
Uncertain
0.086
D
MetaRNN
Uncertain
0.61
D
MetaSVM
Uncertain
-0.24
T
MutationAssessor
Benign
1.8
L
PhyloP100
3.6
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-2.1
N
REVEL
Uncertain
0.50
Sift
Benign
0.20
T
Sift4G
Benign
0.17
T
Polyphen
0.77
P
Vest4
0.32
MutPred
0.77
Loss of glycosylation at S172 (P = 0.0362);
MVP
0.93
MPC
0.96
ClinPred
0.86
D
GERP RS
5.1
Varity_R
0.43
gMVP
0.73
Mutation Taster
=39/61
disease causing

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; API