chr4-103719946-G-A

Position:

• chr4-103719946-G-A

Variant summary

Our verdict is Likely benign. Variant got -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

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACR3	NM_001059.3	c.-271C>T		5_prime_UTR_premature_start_codon_gain_variant	1/5	ENST00000304883.3	NP_001050.1
TACR3	NM_001059.3	c.-271C>T		5_prime_UTR_variant	1/5	ENST00000304883.3	NP_001050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TACR3	ENST00000304883.3	c.-271C>T		5_prime_UTR_premature_start_codon_gain_variant	1/5	1	NM_001059.3	ENSP00000303325.2
TACR3	ENST00000304883.3	c.-271C>T		5_prime_UTR_variant	1/5	1	NM_001059.3	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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000581

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.0
DANN	Benign	0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3733631; hg19: chr4-104641103;