rs749136258

Variant names:

• chr2-75049527-G-A
• rs749136258
• NM_001058.4:c.1129C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-75049527-G-A
• chr2-75049527-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001058.4(TACR1):​c.1129C>T​(p.Pro377Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign 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. P377T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TACR1 NM_001058.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.38
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15440768).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR1	NM_001058.4	c.1129C>T	p.Pro377Ser	missense_variant	Exon 5 of 5	ENST00000305249.10	NP_001049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.1129C>T	p.Pro377Ser	missense_variant	Exon 5 of 5	1	NM_001058.4	ENSP00000303522.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	19
DANN	Benign	0.88
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.65	N
PhyloP100		3.4
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.16
Sift	Benign	0.28	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.17		Gain of phosphorylation at P377 (P = 0.0209);
MVP		0.65
MPC		0.25
ClinPred		0.61	D
GERP RS		4.8
Varity_R		0.090
gMVP		0.28
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs749136258; hg19: chr2-75276654;