Variant 12-57010271-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_013251.4(TAC3):c.*19C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 448,830 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 41 hom., cov: 32)

Exomes 𝑓: 0.020 ( 98 hom. )

Consequence

TAC3
NM_013251.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.860

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 12-57010271-G-A is Benign according to our data. Variant chr12-57010271-G-A is described in ClinVar as [Benign]. Clinvar id is 1294258.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0183 (2782/152114) while in subpopulation NFE AF= 0.0266 (1810/67992). AF 95% confidence interval is 0.0256. There are 41 homozygotes in gnomad4. There are 1433 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAC3	NM_013251.4 linkuse as main transcript	c.*19C>T		3_prime_UTR_variant	7/7	ENST00000458521.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAC3	ENST00000458521.7 linkuse as main transcript	c.*19C>T		3_prime_UTR_variant	7/7	1	NM_013251.4	P1	Q9UHF0-1

Frequencies

GnomAD3 genomes

AF:

0.0183

AC:

2783

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00396

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00727

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00520

Gnomad FIN

AF:

0.0568

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0266

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0161

AC:

2049

AN:

127128

Hom.:

AF XY:

0.0161

AC XY:

1116

AN XY:

69358

show subpopulations

Gnomad AFR exome

AF:

0.00498

Gnomad AMR exome

AF:

0.00544

Gnomad ASJ exome

AF:

0.0128

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00709

Gnomad FIN exome

AF:

0.0652

Gnomad NFE exome

AF:

0.0253

Gnomad OTH exome

AF:

0.0169

GnomAD4 exome

AF:

0.0205

AC:

6080

AN:

296716

Hom.:

Cov.:

AF XY:

0.0191

AC XY:

3229

AN XY:

168864

show subpopulations

Gnomad4 AFR exome

AF:

0.00404

Gnomad4 AMR exome

AF:

0.00546

Gnomad4 ASJ exome

AF:

0.0134

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00701

Gnomad4 FIN exome

AF:

0.0693

Gnomad4 NFE exome

AF:

0.0269

Gnomad4 OTH exome

AF:

0.0220

GnomAD4 genome

AF:

0.0183

AC:

2782

AN:

152114

Hom.:

Cov.:

AF XY:

0.0193

AC XY:

1433

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00395

Gnomad4 AMR

AF:

0.00726

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00520

Gnomad4 FIN

AF:

0.0568

Gnomad4 NFE

AF:

0.0266

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0237

Hom.:

Bravo

AF:

0.0140

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.1

DANN

Benign

0.71

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

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