4-103589504-CAT-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BS1_Supporting

The NM_001059.3(TACR3):c.*176_*177del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 630,088 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: TACR3 NM_001059.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.06

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-AS1 (HGNC:55593): (TACR3 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000138 (21/152182) while in subpopulation EAS AF= 0.00212 (11/5188). AF 95% confidence interval is 0.00119. There are 0 homozygotes in gnomad4. There are 16 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TACR3	NM_001059.3	c.*176_*177del		3_prime_UTR_variant	5/5	ENST00000304883.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TACR3	ENST00000304883.3	c.*176_*177del		3_prime_UTR_variant	5/5	1	NM_001059.3	P1
TACR3-AS1	ENST00000502936.1	n.190-1702_190-1701del		intron_variant, non_coding_transcript_variant		2
TACR3-AS1	ENST00000512401.5	n.292-1702_292-1701del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152064 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000849

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000172 AC: 82 AN: 477906 Hom.: 0 AF XY: 0.000177 AC XY: 44 AN XY: 248160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00203

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000547

Gnomad4 NFE exome AF: 0.00000330

Gnomad4 OTH exome AF: 0.000113

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152182 Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16 AN XY: 74406

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.000849

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000136

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Isolated GnRH Deficiency Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs886058971; hg19: chr4-104510661;