rs3796958

Variant names:

• chr4-103663961-T-C
• rs3796958
• NM_001059.3:c.549-5558A>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.549-5558A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,258 control chromosomes in the GnomAD database, including 1,372 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 (1372 hom., cov: 32)
• Consequence: TACR3 NM_001059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163
• 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: 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR3	NM_001059.3	c.549-5558A>G		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.549-5558A>G		intron_variant	Intron 1 of 4	1	NM_001059.3	ENSP00000303325.2

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18783 AN: 152140 Hom.: 1371 Cov.: 32

Gnomad AFR AF: 0.0762

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0670

Gnomad SAS AF: 0.0754

Gnomad FIN AF: 0.0722

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.123 AC: 18789 AN: 152258 Hom.: 1372 Cov.: 32 AF XY: 0.118 AC XY: 8750 AN XY: 74436

African (AFR) AF: 0.0763 AC: 3172 AN: 41556

American (AMR) AF: 0.113 AC: 1734 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3468

East Asian (EAS) AF: 0.0670 AC: 348 AN: 5194

South Asian (SAS) AF: 0.0749 AC: 362 AN: 4834

European-Finnish (FIN) AF: 0.0722 AC: 766 AN: 10612

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11425 AN: 67990

Other (OTH) AF: 0.133 AC: 281 AN: 2112

Alfa AF: 0.136 Hom.: 173

Bravo AF: 0.124

Asia WGS AF: 0.0960 AC: 338 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.50
PhyloP100		0.16
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: rs3796958; hg19: chr4-104585118;