Genetic Variant TACR1:p.Arg235Gly (chr2-75053637-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001058.4(TACR1):c.703C>G(p.Arg235Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000251 in 1,590,508 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. R235C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TACR1
NM_001058.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.81

Publications

0 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]

TACR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001058.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR1	NM_001058.4	MANE Select	c.703C>G	p.Arg235Gly	missense	Exon 3 of 5	NP_001049.1	P25103-1
	TACR1	NM_015727.3		c.703C>G	p.Arg235Gly	missense	Exon 3 of 4	NP_056542.1	P25103-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR1	ENST00000305249.10	TSL:1 MANE Select	c.703C>G	p.Arg235Gly	missense	Exon 3 of 5	ENSP00000303522.4	P25103-1
	TACR1	ENST00000409848.3	TSL:1	c.703C>G	p.Arg235Gly	missense	Exon 3 of 4	ENSP00000386448.3	P25103-3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152118

Hom.:

Cov.:

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1438390

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

712966

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32828

American (AMR)

AF:

0.00

AC:

AN:

42222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24426

East Asian (EAS)

AF:

0.00

AC:

AN:

39216

South Asian (SAS)

AF:

0.00

AC:

AN:

81922

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5622

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1100176

Other (OTH)

AF:

0.00

AC:

AN:

59362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41420

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Uncertain

0.085

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.77

Eigen

Benign

-0.021

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.72

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

4.8

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.25

Sift

Benign

0.32

Sift4G

Benign

0.14

Polyphen

0.15

Vest4

0.76

MutPred

0.45

Loss of stability (P = 0.0332)

MVP

0.27

MPC

0.89

ClinPred

0.98

GERP RS

4.1

Varity_R

0.68

gMVP

0.74

Mutation Taster

=22/78

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over