rs144292455

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001059.3(TACR3):​c.824G>T​(p.Trp275Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,918 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.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TACR3
NM_001059.3 missense

Scores

12
5
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.97
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.899

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TACR3NM_001059.3 linkc.824G>T p.Trp275Leu missense_variant Exon 3 of 5 ENST00000304883.3 NP_001050.1 P29371

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TACR3ENST00000304883.3 linkc.824G>T p.Trp275Leu missense_variant Exon 3 of 5 1 NM_001059.3 ENSP00000303325.2 P29371

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460918
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726780
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.81
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.65
D
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.88
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Uncertain
0.15
D
MetaRNN
Pathogenic
0.90
D
MetaSVM
Benign
-0.43
T
MutationAssessor
Pathogenic
3.4
M
PrimateAI
Uncertain
0.78
T
PROVEAN
Pathogenic
-12
D
REVEL
Uncertain
0.51
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.84
MutPred
0.62
Gain of disorder (P = 0.1231);
MVP
0.85
MPC
1.5
ClinPred
1.0
D
GERP RS
5.5
Varity_R
0.98
gMVP
0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-104577415; API