2-75053621-A-C

Variant names:

• chr2-75053621-A-C
• rs148906237
• NM_001058.4:c.719T>G

Variant summary

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

The NM_001058.4(TACR1):​c.719T>G​(p.Val240Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,406,816 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. V240A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TACR1 NM_001058.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.22
• 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 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.719T>G	p.Val240Gly	missense_variant	Exon 3 of 5	ENST00000305249.10	NP_001049.1
TACR1	NM_015727.3	c.719T>G	p.Val240Gly	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.719T>G	p.Val240Gly	missense_variant	Exon 3 of 5	1	NM_001058.4	ENSP00000303522.4
TACR1	ENST00000409848.3	c.719T>G	p.Val240Gly	missense_variant	Exon 3 of 4	1		ENSP00000386448.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1406816 Hom.: 0 Cov.: 30 AF XY: 0.00000288 AC XY: 2 AN XY: 693828

African (AFR) AF: 0.00 AC: 0 AN: 31620

American (AMR) AF: 0.00 AC: 0 AN: 37528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22782

East Asian (EAS) AF: 0.00 AC: 0 AN: 38412

South Asian (SAS) AF: 0.00 AC: 0 AN: 76334

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5458

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1085246

Other (OTH) AF: 0.00 AC: 0 AN: 57904

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.78	D;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	1.5	L;L
PhyloP100		9.2
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.4	D;D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.98	D;.
Vest4		0.53
MutPred		0.50		Gain of disorder (P = 0.0374);Gain of disorder (P = 0.0374);
MVP		0.98
MPC		0.92
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.88
gMVP		0.89
Mutation Taster		=30/70	disease causing

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: rs148906237; hg19: chr2-75280748;