12-57015455-G-A

Variant names:

• chr12-57015455-G-A
• rs17119330
• NM_013251.4:c.114+229C>T

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.114+229C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0906 in 152,112 control chromosomes in the GnomAD database, including 664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.091 (664 hom., cov: 31)
• Consequence: TAC3 NM_013251.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.244

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=-0.76).
• BP6: Variant 12-57015455-G-A is Benign according to our data. Variant chr12-57015455-G-A is described in ClinVar as [Benign]. Clinvar id is 677241.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAC3	NM_013251.4	c.114+229C>T		intron_variant	Intron 2 of 6	ENST00000458521.7	NP_037383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAC3	ENST00000458521.7	c.114+229C>T		intron_variant	Intron 2 of 6	1	NM_013251.4	ENSP00000404056.2
TAC3	ENST00000300108.7	n.114+229C>T		intron_variant	Intron 2 of 8	2		ENSP00000300108.3
TAC3	ENST00000379411.6	n.114+229C>T		intron_variant	Intron 2 of 7	2		ENSP00000368721.2
TAC3	ENST00000393867.5	n.114+229C>T		intron_variant	Intron 2 of 9	2		ENSP00000377445.1

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13772 AN: 151994 Hom.: 665 Cov.: 31

Gnomad AFR AF: 0.0816

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0743

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.0821

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

GnomAD4 genome AF: 0.0906 AC: 13779 AN: 152112 Hom.: 664 Cov.: 31 AF XY: 0.0934 AC XY: 6947 AN XY: 74352

Gnomad4 AFR AF: 0.0815

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.0743

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0811

Gnomad4 OTH AF: 0.0836

Alfa AF: 0.0824 Hom.: 353

Bravo AF: 0.0899

Asia WGS AF: 0.135 AC: 466 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.7
DANN	Benign	0.68

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: rs17119330; hg19: chr12-57409239;