chr4-103719946-G-A

Variant names:

• chr4-103719946-G-A
• rs3733631
• NM_001059.3:c.-271C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001059.3(TACR3):​c.-271C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 403,980 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: TACR3 NM_001059.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932
• Publications: 22 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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.-271C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_001050.1
	TACR3	NM_001059.3	MANE Select	c.-271C>T		5_prime_UTR	Exon 1 of 5	NP_001050.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR3	ENST00000304883.3	TSL:1 MANE Select	c.-271C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000303325.2
	TACR3	ENST00000304883.3	TSL:1 MANE Select	c.-271C>T		5_prime_UTR	Exon 1 of 5	ENSP00000303325.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000248 AC: 1 AN: 403980 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 210832

African (AFR) AF: 0.00 AC: 0 AN: 11820

American (AMR) AF: 0.0000581 AC: 1 AN: 17212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12680

East Asian (EAS) AF: 0.00 AC: 0 AN: 28584

South Asian (SAS) AF: 0.00 AC: 0 AN: 39320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1816

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 242462

Other (OTH) AF: 0.00 AC: 0 AN: 23852

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 271

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.0
DANN	Benign	0.95
PhyloP100		-0.93
PromoterAI		-0.10	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3733631; hg19: chr4-104641103;