4-103589807-G-C

Variant names:

• chr4-103589807-G-C
• rs767138892
• NM_001059.3:c.1273C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001059.3(TACR3):​c.1273C>G​(p.Arg425Gly) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TACR3 NM_001059.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.095454544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR3	NM_001059.3	c.1273C>G	p.Arg425Gly	missense_variant	Exon 5 of 5	ENST00000304883.3	NP_001050.1
TACR3-AS1	NR_186501.1	n.190-1400G>C		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR3	ENST00000304883.3	c.1273C>G	p.Arg425Gly	missense_variant	Exon 5 of 5	1	NM_001059.3	ENSP00000303325.2
TACR3-AS1	ENST00000502936.1	n.190-1400G>C		intron_variant	Intron 2 of 4	2
TACR3-AS1	ENST00000512401.5	n.292-1400G>C		intron_variant	Intron 3 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.12
Sift	Benign	0.34	T
Sift4G	Benign	0.36	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.29		Gain of glycosylation at S423 (P = 0.0048);
MVP		0.79
MPC		0.41
ClinPred		0.15	T
GERP RS		3.8
Varity_R		0.092
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs767138892; hg19: chr4-104510964;