4-103674225-A-G

Variant names:

• chr4-103674225-A-G
• rs12649621
• NM_001059.3:c.549-15822T>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.549-15822T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 151,974 control chromosomes in the GnomAD database, including 2,348 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 0.15 (2348 hom., cov: 32)
• Consequence: TACR3 NM_001059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 1 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 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.549-15822T>C		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.549-15822T>C		intron	N/A	ENSP00000303325.2	P29371

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23402 AN: 151856 Hom.: 2344 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0878

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.154 AC: 23427 AN: 151974 Hom.: 2348 Cov.: 32 AF XY: 0.160 AC XY: 11893 AN XY: 74282

African (AFR) AF: 0.225 AC: 9332 AN: 41448

American (AMR) AF: 0.156 AC: 2387 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 357 AN: 3468

East Asian (EAS) AF: 0.431 AC: 2220 AN: 5148

South Asian (SAS) AF: 0.258 AC: 1244 AN: 4814

European-Finnish (FIN) AF: 0.134 AC: 1415 AN: 10530

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0878 AC: 5965 AN: 67974

Other (OTH) AF: 0.162 AC: 342 AN: 2114

Alfa AF: 0.0513 Hom.: 49

Bravo AF: 0.158

Asia WGS AF: 0.311 AC: 1082 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.31
DANN	Benign	0.47
PhyloP100		-1.1
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: rs12649621; hg19: chr4-104595382;