2-75198602-A-T

Variant names:

• chr2-75198602-A-T
• rs6715729
• NM_001058.4:c.333T>A

Variant summary

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

The NM_001058.4(TACR1):​c.333T>A​(p.Phe111Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: TACR1 NM_001058.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12

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]

LOC105374811 (HGNC:):

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.333T>A	p.Phe111Leu	missense_variant	Exon 1 of 5	ENST00000305249.10	NP_001049.1
TACR1	NM_015727.3	c.333T>A	p.Phe111Leu	missense_variant	Exon 1 of 4		NP_056542.1
LOC105374811	NR_168009.1	n.372+42287A>T		intron_variant	Intron 2 of 3
LOC105374811	NR_168010.1	n.366+42287A>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR1	ENST00000305249.10	c.333T>A	p.Phe111Leu	missense_variant	Exon 1 of 5	1	NM_001058.4	ENSP00000303522.4
TACR1	ENST00000409848.3	c.333T>A	p.Phe111Leu	missense_variant	Exon 1 of 4	1		ENSP00000386448.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152056 Hom.: 0 Cov.: 33 FAILED QC

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 58

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152056 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74246

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;.
Eigen	Benign	0.044
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.28
Sift	Benign	0.050	D;T
Sift4G	Benign	0.14	T;T
Polyphen		0.86	P;.
Vest4		0.82
MutPred		0.45		Loss of stability (P = 0.1672);Loss of stability (P = 0.1672);
MVP		0.38
MPC		0.89
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.42
gMVP		0.73

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: rs6715729; hg19: chr2-75425728;