rs199807268

Variant names:

• chr4-103589758-C-A
• rs199807268
• NM_001059.3:c.1322G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-103589758-C-A
• chr4-103589758-C-G
• chr4-103589758-C-T

Variant summary

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

The NM_001059.3(TACR3):​c.1322G>T​(p.Arg441Leu) 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. 15/22 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. R441C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TACR3 NM_001059.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262
• Publications: 2 publications found

Genes affected

TACR3 (HGNC:11528): (tachykinin receptor 3) This gene belongs to a family of genes that function as receptors for tachykinins. Receptor affinities are specified by variations in the 5'-end of the sequence. The receptors belonging to this family are characterized by interactions with G proteins and 7 hydrophobic transmembrane regions. This gene encodes the receptor for the tachykinin neurokinin 3, also referred to as neurokinin B. [provided by RefSeq, Jul 2008]

TACR3-AS1 (HGNC:55593): (TACR3 antisense RNA 1)

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=0.08848056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR3	NM_001059.3	c.1322G>T	p.Arg441Leu	missense_variant	Exon 5 of 5	ENST00000304883.3	NP_001050.1
TACR3-AS1	NR_186501.1	n.190-1449C>A		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR3	ENST00000304883.3	c.1322G>T	p.Arg441Leu	missense_variant	Exon 5 of 5	1	NM_001059.3	ENSP00000303325.2
TACR3-AS1	ENST00000502936.1	n.190-1449C>A		intron_variant	Intron 2 of 4	2
TACR3-AS1	ENST00000512401.5	n.292-1449C>A		intron_variant	Intron 3 of 4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		-0.26
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.052
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.20	T
Polyphen		0.049	B
Vest4		0.23
MutPred		0.34		Gain of glycosylation at S444 (P = 0.0056);
MVP		0.78
MPC		0.41
ClinPred		0.60	D
GERP RS		2.9
Varity_R		0.097
gMVP		0.42
Mutation Taster		=91/9	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: rs199807268; hg19: chr4-104510915; COSMIC: COSV59206890;