rs1905173

Variant names:

• chr4-103714945-T-A
• rs1905173
• NM_001059.3:c.548+4183A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-103714945-T-A
• chr4-103714945-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001059.3(TACR3):​c.548+4183A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,146 control chromosomes in the GnomAD database, including 1,357 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1357 hom., cov: 32)
• Consequence: TACR3 NM_001059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• 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 Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism 11 with or without anosmia

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR3	NM_001059.3	c.548+4183A>T		intron_variant	Intron 1 of 4	ENST00000304883.3	NP_001050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR3	ENST00000304883.3	c.548+4183A>T		intron_variant	Intron 1 of 4	1	NM_001059.3	ENSP00000303325.2

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17767 AN: 152030 Hom.: 1357 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0871

Gnomad OTH AF: 0.127

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.117 AC: 17776 AN: 152146 Hom.: 1357 Cov.: 32 AF XY: 0.125 AC XY: 9278 AN XY: 74372

African (AFR) AF: 0.102 AC: 4244 AN: 41524

American (AMR) AF: 0.143 AC: 2188 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3466

East Asian (EAS) AF: 0.371 AC: 1913 AN: 5160

South Asian (SAS) AF: 0.270 AC: 1299 AN: 4814

European-Finnish (FIN) AF: 0.134 AC: 1423 AN: 10594

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0871 AC: 5920 AN: 67974

Other (OTH) AF: 0.129 AC: 273 AN: 2114

Alfa AF: 0.0447 Hom.: 35

Bravo AF: 0.114

Asia WGS AF: 0.294 AC: 1020 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.9
DANN	Benign	0.70
PhyloP100		0.042
Mutation Taster		=100/0	polymorphism (auto)

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: rs1905173; hg19: chr4-104636102;