NM_001059.3:c.549-3373C>G

Variant names:

• chr4-103661776-G-C
• rs11725038
• NM_001059.3:c.549-3373C>G

Variant summary

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

The NM_001059.3(TACR3):​c.549-3373C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,908 control chromosomes in the GnomAD database, including 14,753 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 0.41 (14753 hom., cov: 31)
• Consequence: TACR3 NM_001059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• 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: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

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.549-3373C>G		intron	N/A	NP_001050.1	P29371

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR3	ENST00000304883.3	TSL:1 MANE Select	c.549-3373C>G		intron	N/A	ENSP00000303325.2	P29371

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62175 AN: 151790 Hom.: 14714 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.410 AC: 62264 AN: 151908 Hom.: 14753 Cov.: 31 AF XY: 0.401 AC XY: 29797 AN XY: 74246

African (AFR) AF: 0.664 AC: 27522 AN: 41420

American (AMR) AF: 0.323 AC: 4936 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1068 AN: 3470

East Asian (EAS) AF: 0.258 AC: 1330 AN: 5152

South Asian (SAS) AF: 0.297 AC: 1432 AN: 4814

European-Finnish (FIN) AF: 0.239 AC: 2518 AN: 10548

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22145 AN: 67926

Other (OTH) AF: 0.398 AC: 841 AN: 2112

Alfa AF: 0.182 Hom.: 309

Bravo AF: 0.426

Asia WGS AF: 0.310 AC: 1079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.79
PhyloP100		0.011
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: rs11725038; hg19: chr4-104582933;