rs17033889

Variant names:

• chr4-103589735-C-A
• rs17033889
• NM_001059.3:c.1345G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-103589735-C-A
• chr4-103589735-C-G
• chr4-103589735-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001059.3(TACR3):​c.1345G>T​(p.Ala449Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000301 in 1,613,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A449T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00031 (0 hom.)
• Consequence: TACR3 NM_001059.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:6
• Conservation: PhyloP100: 2.19
• Publications: 16 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.050845176).

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.1345G>T	p.Ala449Ser	missense	Exon 5 of 5	NP_001050.1	P29371
	TACR3-AS1	NR_186501.1		n.190-1472C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR3	ENST00000304883.3	TSL:1 MANE Select	c.1345G>T	p.Ala449Ser	missense	Exon 5 of 5	ENSP00000303325.2	P29371
	TACR3-AS1	ENST00000502936.1	TSL:2	n.190-1472C>A		intron	N/A
	TACR3-AS1	ENST00000512401.5	TSL:2	n.292-1472C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152096 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000456

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000167 AC: 42 AN: 251110 AF XY: 0.000177

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000326

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000308 AC: 450 AN: 1461664 Hom.: 0 Cov.: 32 AF XY: 0.000286 AC XY: 208 AN XY: 727132

African (AFR) AF: 0.0000897 AC: 3 AN: 33456

American (AMR) AF: 0.0000447 AC: 2 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000387 AC: 430 AN: 1111862

Other (OTH) AF: 0.000199 AC: 12 AN: 60378

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152096 Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15 AN XY: 74278

African (AFR) AF: 0.0000483 AC: 2 AN: 41418

American (AMR) AF: 0.000131 AC: 2 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000257 Hom.: 11

Bravo AF: 0.000208

ExAC AF: 0.000132 AC: 16

EpiCase AF: 0.000382

EpiControl AF: 0.000178

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	3	-	not provided (3)
-	2	-	Hypogonadotropic hypogonadism 11 with or without anosmia (2)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.084	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.2
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.59	N
REVEL	Benign	0.051
Sift	Benign	0.40	T
Sift4G	Benign	0.75	T
Polyphen		0.022	B
Vest4		0.086
MVP		0.78
MPC		0.30
ClinPred		0.022	T
GERP RS		4.5
Varity_R		0.054
gMVP		0.36
Mutation Taster		=88/12	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: rs17033889; hg19: chr4-104510892;