Genetic Variant TACR1:p.Arg235Ser (chr2-75053637-G-T) – 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>A(p.Arg235Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000348 in 1,438,390 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: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 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:

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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;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR1	NM_001058.4 link	c.703C>A	p.Arg235Ser	missense_variant	Exon 3 of 5	ENST00000305249.10	NP_001049.1	P25103-1
TACR1	NM_015727.3 link	c.703C>A	p.Arg235Ser	missense_variant	Exon 3 of 4		NP_056542.1	P25103-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10 link	c.703C>A	p.Arg235Ser	missense_variant	Exon 3 of 5	1	NM_001058.4	ENSP00000303522.4		P25103-1
TACR1	ENST00000409848.3 link	c.703C>A	p.Arg235Ser	missense_variant	Exon 3 of 4	1		ENSP00000386448.3		P25103-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000428

AC:

AN:

233708

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:

0.00000936

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000348

AC:

AN:

1438390

Hom.:

Cov.:

AF XY:

0.00000421

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:

0.00000364

AC:

AN:

1100176

Other (OTH)

AF:

0.0000168

AC:

AN:

59362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Uncertain

0.063

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.73

D;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.46

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L

PhyloP100

4.8

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.24

Sift

Benign

0.039

D;D

Sift4G

Uncertain

0.030

D;D

Polyphen

0.84

P;.

Vest4

0.56

MutPred

0.46

Loss of catalytic residue at R235 (P = 0.0059);Loss of catalytic residue at R235 (P = 0.0059);

MVP

0.34

MPC

0.79

ClinPred

0.95

GERP RS

4.1

Varity_R

0.69

gMVP

0.76

Mutation Taster

=25/75

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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2-75053637-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over