chr4-103589707-T-C

Variant names:

• chr4-103589707-T-C
• rs1723849531
• NM_001059.3:c.1373A>G

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.1373A>G​(p.Tyr458Cys) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TACR3 NM_001059.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56
• Publications: 0 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=0.22798467).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001059.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR3	NM_001059.3	MANE Select	c.1373A>G	p.Tyr458Cys	missense	Exon 5 of 5	NP_001050.1	P29371
	TACR3-AS1	NR_186501.1		n.190-1500T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR3	ENST00000304883.3	TSL:1 MANE Select	c.1373A>G	p.Tyr458Cys	missense	Exon 5 of 5	ENSP00000303325.2	P29371
	TACR3-AS1	ENST00000502936.1	TSL:2	n.190-1500T>C		intron	N/A
	TACR3-AS1	ENST00000512401.5	TSL:2	n.292-1500T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.048
Eigen_PC	Benign	0.043
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.6
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.13
Sift	Benign	0.11	T
Sift4G	Benign	0.13	T
Polyphen		0.95	P
Vest4		0.20
MutPred		0.15		Gain of glycosylation at S460 (P = 0.0074)
MVP		0.93
MPC		0.69
ClinPred		0.69	D
GERP RS		4.5
Varity_R		0.14
gMVP		0.28
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1723849531; hg19: chr4-104510864;