4-103666820-C-T

Variant names:

• chr4-103666820-C-T
• rs1351623
• NM_001059.3:c.549-8417G>A

Variant summary

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

The NM_001059.3(TACR3):​c.549-8417G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,012 control chromosomes in the GnomAD database, including 14,188 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 0.35 (14188 hom., cov: 32)
• Consequence: TACR3 NM_001059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR3	NM_001059.3	MANE Select	c.549-8417G>A		intron	N/A	NP_001050.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR3	ENST00000304883.3	TSL:1 MANE Select	c.549-8417G>A		intron	N/A	ENSP00000303325.2

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53412 AN: 151894 Hom.: 14142 Cov.: 32

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.352 AC: 53518 AN: 152012 Hom.: 14188 Cov.: 32 AF XY: 0.350 AC XY: 26027 AN XY: 74314

African (AFR) AF: 0.744 AC: 30847 AN: 41460

American (AMR) AF: 0.266 AC: 4054 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 625 AN: 3470

East Asian (EAS) AF: 0.433 AC: 2237 AN: 5166

South Asian (SAS) AF: 0.321 AC: 1544 AN: 4814

European-Finnish (FIN) AF: 0.167 AC: 1766 AN: 10560

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11505 AN: 67958

Other (OTH) AF: 0.325 AC: 685 AN: 2110

Alfa AF: 0.258 Hom.: 2747

Bravo AF: 0.374

Asia WGS AF: 0.378 AC: 1316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.1
DANN	Benign	0.48
PhyloP100		0.23
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: rs1351623; hg19: chr4-104587977;