12-57016407-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013251.4(TAC3):c.-26C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0903 in 451,378 control chromosomes in the GnomAD database, including 2,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.090 (664 hom., cov: 31)
  • Exomes 𝑓: 0.090 (1369 hom.)
• Consequence: TAC3 NM_013251.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.258

Genes affected

TAC3 (HGNC:11521): (tachykinin precursor 3) This gene encodes a member of the tachykinin family of secreted neuropeptides. The encoded preproprotein is proteolytically processed to generate the mature peptide, which is primarily expressed in the central and peripheral nervous systems and functions as a neurotransmitter. This peptide is the ligand for the neurokinin-3 receptor. This protein is also expressed in the outer syncytiotrophoblast of the placenta and may be associated with pregnancy-induced hypertension and pre-eclampsia. Mutations in this gene are associated with normosmic hypogonadotropic hypogonadism. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 12-57016407-G-A is Benign according to our data. Variant chr12-57016407-G-A is described in ClinVar as [Benign]. Clinvar id is 1269499.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAC3	NM_013251.4	c.-26C>T		5_prime_UTR_variant	1/7	ENST00000458521.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAC3	ENST00000458521.7	c.-26C>T		5_prime_UTR_variant	1/7	1	NM_013251.4	P1

Frequencies

GnomAD3 genomes AF: 0.0901 AC: 13700 AN: 152018 Hom.: 663 Cov.: 31

Gnomad AFR AF: 0.0813

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0729

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0804

Gnomad OTH AF: 0.0817

GnomAD3 exomes AF: 0.0958 AC: 12912 AN: 134772 Hom.: 718 AF XY: 0.0954 AC XY: 6974 AN XY: 73084

Gnomad AFR exome AF: 0.0803

Gnomad AMR exome AF: 0.0921

Gnomad ASJ exome AF: 0.0762

Gnomad EAS exome AF: 0.187

Gnomad SAS exome AF: 0.0983

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.0826

Gnomad OTH exome AF: 0.0917

GnomAD4 exome AF: 0.0904 AC: 27052 AN: 299242 Hom.: 1369 Cov.: 0 AF XY: 0.0902 AC XY: 15358 AN XY: 170224

Gnomad4 AFR exome AF: 0.0811

Gnomad4 AMR exome AF: 0.0929

Gnomad4 ASJ exome AF: 0.0727

Gnomad4 EAS exome AF: 0.178

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.0985

Gnomad4 NFE exome AF: 0.0824

Gnomad4 OTH exome AF: 0.0862

GnomAD4 genome AF: 0.0901 AC: 13710 AN: 152136 Hom.: 664 Cov.: 31 AF XY: 0.0929 AC XY: 6910 AN XY: 74384

Gnomad4 AFR AF: 0.0812

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.0729

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.0804

Gnomad4 OTH AF: 0.0851

Alfa AF: 0.0801 Hom.: 191

Bravo AF: 0.0894

Asia WGS AF: 0.140 AC: 483 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.5
Dann	Benign	0.74

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: rs2291855; hg19: chr12-57410191;