NM_001059.3:c.888+24664C>T

Variant names:

• chr4-103631530-G-A
• rs12641703
• NM_001059.3:c.888+24664C>T

Variant summary

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

The NM_001059.3(TACR3):​c.888+24664C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 151,978 control chromosomes in the GnomAD database, including 29,663 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 0.60 (29663 hom., cov: 31)
• Consequence: TACR3 NM_001059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• 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: 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 = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR3	NM_001059.3	c.888+24664C>T		intron_variant	Intron 3 of 4	ENST00000304883.3	NP_001050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR3	ENST00000304883.3	c.888+24664C>T		intron_variant	Intron 3 of 4	1	NM_001059.3	ENSP00000303325.2

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91420 AN: 151860 Hom.: 29612 Cov.: 31

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.602 AC: 91519 AN: 151978 Hom.: 29663 Cov.: 31 AF XY: 0.597 AC XY: 44357 AN XY: 74248

African (AFR) AF: 0.845 AC: 35076 AN: 41504

American (AMR) AF: 0.453 AC: 6915 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2063 AN: 3466

East Asian (EAS) AF: 0.335 AC: 1722 AN: 5144

South Asian (SAS) AF: 0.507 AC: 2445 AN: 4822

European-Finnish (FIN) AF: 0.532 AC: 5596 AN: 10522

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35721 AN: 67944

Other (OTH) AF: 0.608 AC: 1281 AN: 2106

Alfa AF: 0.548 Hom.: 27454

Bravo AF: 0.606

Asia WGS AF: 0.479 AC: 1668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.35
PhyloP100		-1.6
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: rs12641703; hg19: chr4-104552687;