chr12-57015455-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

TAC3 Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism 10 with or without anosmia

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013251.4. 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
	TAC3	NM_013251.4	MANE Select	c.114+229C>T		intron	N/A	NP_037383.1	Q9UHF0-1
	TAC3	NM_001178054.2		c.114+229C>T		intron	N/A	NP_001171525.1	Q9UHF0-3
	TAC3	NR_033654.2		n.262+229C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAC3	ENST00000458521.7	TSL:1 MANE Select	c.114+229C>T		intron	N/A	ENSP00000404056.2	Q9UHF0-1
	TAC3	ENST00000441881.5	TSL:1	c.114+229C>T		intron	N/A	ENSP00000408208.1	Q9UHF0-3
	TAC3	ENST00000300108.7	TSL:2	n.114+229C>T		intron	N/A	ENSP00000300108.3	Q9UHF0-1

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

African (AFR) AF: 0.0815 AC: 3382 AN: 41490

American (AMR) AF: 0.119 AC: 1815 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0743 AC: 258 AN: 3472

East Asian (EAS) AF: 0.182 AC: 937 AN: 5162

South Asian (SAS) AF: 0.106 AC: 513 AN: 4818

European-Finnish (FIN) AF: 0.106 AC: 1121 AN: 10596

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0811 AC: 5510 AN: 67972

Other (OTH) AF: 0.0836 AC: 177 AN: 2116

Alfa AF: 0.0829 Hom.: 422

Bravo AF: 0.0899

Asia WGS AF: 0.135 AC: 466 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.7
DANN	Benign	0.68
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17119330; hg19: chr12-57409239;