2-75053621-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001058.4(TACR1):​c.719T>A​(p.Val240Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000257 in 1,558,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. V240A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TACR1
NM_001058.4 missense

Scores

5
10
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.22

Publications

4 publications found
Variant links:
Genes affected
TACR1 (HGNC:11526): (tachykinin receptor 1) This gene belongs to a gene family of tachykinin receptors. These tachykinin receptors are characterized by interactions with G proteins and contain seven hydrophobic transmembrane regions. This gene encodes the receptor for the tachykinin substance P, also referred to as neurokinin 1. The encoded protein is also involved in the mediation of phosphatidylinositol metabolism of substance P. [provided by RefSeq, Sep 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.768

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TACR1NM_001058.4 linkc.719T>A p.Val240Asp missense_variant Exon 3 of 5 ENST00000305249.10 NP_001049.1 P25103-1
TACR1NM_015727.3 linkc.719T>A p.Val240Asp missense_variant Exon 3 of 4 NP_056542.1 P25103-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TACR1ENST00000305249.10 linkc.719T>A p.Val240Asp missense_variant Exon 3 of 5 1 NM_001058.4 ENSP00000303522.4 P25103-1
TACR1ENST00000409848.3 linkc.719T>A p.Val240Asp missense_variant Exon 3 of 4 1 ENSP00000386448.3 P25103-3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152114
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000213
AC:
3
AN:
1406816
Hom.:
0
Cov.:
30
AF XY:
0.00000288
AC XY:
2
AN XY:
693828
show subpopulations
African (AFR)
AF:
0.0000949
AC:
3
AN:
31620
American (AMR)
AF:
0.00
AC:
0
AN:
37528
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22782
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38412
South Asian (SAS)
AF:
0.00
AC:
0
AN:
76334
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51532
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5458
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1085246
Other (OTH)
AF:
0.00
AC:
0
AN:
57904
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
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:
152114
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74300
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
41394
American (AMR)
AF:
0.0000654
AC:
1
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5194
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10606
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68024
Other (OTH)
AF:
0.00
AC:
0
AN:
2086
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.85
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Pathogenic
29
DANN
Benign
0.97
DEOGEN2
Uncertain
0.78
D;.
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.97
D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.77
D;D
MetaSVM
Benign
-0.60
T
MutationAssessor
Benign
1.3
L;L
PhyloP100
9.2
PrimateAI
Uncertain
0.66
T
PROVEAN
Pathogenic
-5.2
D;D
REVEL
Uncertain
0.56
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
0.35
B;.
Vest4
0.69
MutPred
0.58
Gain of disorder (P = 0.0299);Gain of disorder (P = 0.0299);
MVP
0.86
MPC
1.0
ClinPred
1.0
D
GERP RS
5.0
Varity_R
0.93
gMVP
0.95
Mutation Taster
=26/74
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: rs148906237; hg19: chr2-75280748; API