2-75053736-C-T

Variant names:

• chr2-75053736-C-T
• rs771674417
• NM_001058.4:c.604G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001058.4(TACR1):​c.604G>A​(p.Val202Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: TACR1 NM_001058.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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

Verdict is Uncertain_significance. Variant got 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	c.604G>A	p.Val202Met	missense_variant	Exon 3 of 5	ENST00000305249.10	NP_001049.1
TACR1	NM_015727.3	c.604G>A	p.Val202Met	missense_variant	Exon 3 of 4		NP_056542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.604G>A	p.Val202Met	missense_variant	Exon 3 of 5	1	NM_001058.4	ENSP00000303522.4
TACR1	ENST00000409848.3	c.604G>A	p.Val202Met	missense_variant	Exon 3 of 4	1		ENSP00000386448.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000239 AC: 6 AN: 251190 Hom.: 0 AF XY: 0.0000295 AC XY: 4 AN XY: 135732

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: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461874 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 727236

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: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T;.
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.28
Sift	Benign	0.042	D;D
Sift4G	Uncertain	0.045	D;D
Polyphen		0.85	P;.
Vest4		0.59
MutPred		0.49		Loss of catalytic residue at V202 (P = 0.075);Loss of catalytic residue at V202 (P = 0.075);
MVP		0.82
MPC		0.28
ClinPred		0.30	T
GERP RS		5.1
Varity_R		0.23
gMVP		0.46

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

LitVar

Other links and lift over

dbSNP: rs771674417; hg19: chr2-75280863;