Variant 12-57012660-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013251.4(TAC3):c.292+162A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0858 in 1,612,812 control chromosomes in the GnomAD database, including 6,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.091 ( 662 hom., cov: 32)

Exomes 𝑓: 0.085 ( 5595 hom. )

Consequence

TAC3
NM_013251.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.27

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-57012660-T-C is Benign according to our data. Variant chr12-57012660-T-C is described in ClinVar as [Benign]. Clinvar id is 675709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAC3	NM_013251.4 link	c.292+162A>G		intron_variant	Intron 5 of 6	ENST00000458521.7	NP_037383.1	Q9UHF0-1A0A024RB47

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TAC3	ENST00000458521.7 link	c.292+162A>G	intron_variant	Intron 5 of 6	1	NM_013251.4	ENSP00000404056.2	Q9UHF0-1
TAC3	ENST00000393867.5 link	n.370A>G	non_coding_transcript_exon_variant	Exon 6 of 10	2		ENSP00000377445.1	Q9UHF0-2
TAC3	ENST00000300108.7 link	n.292+162A>G	intron_variant	Intron 5 of 8	2		ENSP00000300108.3	Q9UHF0-1
TAC3	ENST00000379411.6 link	n.239-208A>G	intron_variant	Intron 4 of 7	2		ENSP00000368721.2	Q9UHF0-3

Frequencies

GnomAD3 genomes

AF:

0.0906

AC:

13771

AN:

152004

Hom.:

663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0817

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.0736

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0811

Gnomad OTH

AF:

0.0818

GnomAD3 exomes

AF:

0.0956

AC:

23992

AN:

250930

Hom.:

1293

AF XY:

0.0955

AC XY:

12955

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.0831

Gnomad AMR exome

AF:

0.0883

Gnomad ASJ exome

AF:

0.0762

Gnomad EAS exome

AF:

0.187

Gnomad SAS exome

AF:

0.101

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.0840

Gnomad OTH exome

AF:

0.0888

GnomAD4 exome

AF:

0.0853

AC:

124527

AN:

1460690

Hom.:

5595

Cov.:

AF XY:

0.0852

AC XY:

61921

AN XY:

726680

show subpopulations

Gnomad4 AFR exome

AF:

0.0833

Gnomad4 AMR exome

AF:

0.0906

Gnomad4 ASJ exome

AF:

0.0742

Gnomad4 EAS exome

AF:

0.140

Gnomad4 SAS exome

AF:

0.102

Gnomad4 FIN exome

AF:

0.103

Gnomad4 NFE exome

AF:

0.0812

Gnomad4 OTH exome

AF:

0.0858

GnomAD4 genome

AF:

0.0906

AC:

13777

AN:

152122

Hom.:

662

Cov.:

AF XY:

0.0933

AC XY:

6938

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0816

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.0736

Gnomad4 EAS

AF:

0.182

Gnomad4 SAS

AF:

0.106

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.0811

Gnomad4 OTH

AF:

0.0833

Alfa

AF:

0.0824

Hom.:

896

Bravo

AF:

0.0900

Asia WGS

AF:

0.135

AC:

468

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

-0.81

CADD

Benign

DANN

Uncertain

0.99

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over