10-69404881-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000373306.5(TACR2):ā€‹c.1142G>Cā€‹(p.Gly381Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000054 in 1,611,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 32)
Exomes š‘“: 0.000055 ( 0 hom. )

Consequence

TACR2
ENST00000373306.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.689
Variant links:
Genes affected
TACR2 (HGNC:11527): (tachykinin receptor 2) 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 neuropeptide substance K, also referred to as neurokinin A. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04060474).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TACR2NM_001057.3 linkuse as main transcriptc.1142G>C p.Gly381Ala missense_variant 5/5 ENST00000373306.5 NP_001048.2 P21452

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TACR2ENST00000373306.5 linkuse as main transcriptc.1142G>C p.Gly381Ala missense_variant 5/51 NM_001057.3 ENSP00000362403.4 P21452
TACR2ENST00000373307.5 linkuse as main transcriptc.506G>C p.Gly169Ala missense_variant 3/32 ENSP00000362404.1 A6NEW7

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152208
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000814
AC:
20
AN:
245730
Hom.:
0
AF XY:
0.000105
AC XY:
14
AN XY:
133038
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 SAS exome
AF:
0.0000331
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000173
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000548
AC:
80
AN:
1459320
Hom.:
0
Cov.:
30
AF XY:
0.0000675
AC XY:
49
AN XY:
725798
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:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000621
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152208
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000283
Hom.:
0
Bravo
AF:
0.0000416
ExAC
AF:
0.0000741
AC:
9

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 21, 2023The c.1142G>C (p.G381A) alteration is located in exon 5 (coding exon 5) of the TACR2 gene. This alteration results from a G to C substitution at nucleotide position 1142, causing the glycine (G) at amino acid position 381 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
0.48
DANN
Benign
0.47
DEOGEN2
Benign
0.025
.;.;T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.56
T;T;T
M_CAP
Benign
0.0056
T
MetaRNN
Benign
0.041
T;T;T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
0.69
.;.;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.030
N;.;N
REVEL
Benign
0.082
Sift
Benign
0.29
T;.;T
Sift4G
Benign
0.28
T;T;T
Polyphen
0.0
.;.;B
Vest4
0.12
MVP
0.28
MPC
0.30
ClinPred
0.14
T
GERP RS
-3.3
Varity_R
0.037
gMVP
0.28

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs149265154; hg19: chr10-71164637; API