rs3796954

Variant names:

• chr4-103679415-A-G
• rs3796954
• NM_001059.3:c.549-21012T>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.549-21012T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 151,826 control chromosomes in the GnomAD database, including 7,063 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 0.24 (7063 hom., cov: 31)
• Consequence: TACR3 NM_001059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469
• Publications: 4 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR3	NM_001059.3	c.549-21012T>C		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.549-21012T>C		intron_variant	Intron 1 of 4	1	NM_001059.3	ENSP00000303325.2

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37107 AN: 151708 Hom.: 7046 Cov.: 31

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0993

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.245 AC: 37170 AN: 151826 Hom.: 7063 Cov.: 31 AF XY: 0.247 AC XY: 18340 AN XY: 74218

African (AFR) AF: 0.516 AC: 21354 AN: 41412

American (AMR) AF: 0.192 AC: 2917 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3462

East Asian (EAS) AF: 0.438 AC: 2259 AN: 5154

South Asian (SAS) AF: 0.280 AC: 1351 AN: 4822

European-Finnish (FIN) AF: 0.135 AC: 1434 AN: 10590

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0992 AC: 6735 AN: 67860

Other (OTH) AF: 0.231 AC: 487 AN: 2108

Alfa AF: 0.154 Hom.: 1590

Bravo AF: 0.259

Asia WGS AF: 0.345 AC: 1198 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.56
DANN	Benign	0.56
PhyloP100		-0.47
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: rs3796954; hg19: chr4-104600572;