chr12-57015597-C-A

Position:

• chr12-57015597-C-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.114+87G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 1,202,076 control chromosomes in the GnomAD database, including 5,001 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.091 (661 hom., cov: 32)
  • Exomes 𝑓: 0.086 (4340 hom.)
• Consequence: TAC3 NM_013251.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.101

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=-0.83).
• BP6: Variant 12-57015597-C-A is Benign according to our data. Variant chr12-57015597-C-A is described in ClinVar as [Benign]. Clinvar id is 677240.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/exons	MANE	UniProt
TAC3	NM_013251.4	c.114+87G>T		intron_variant		ENST00000458521.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAC3	ENST00000458521.7	c.114+87G>T		intron_variant		1	NM_013251.4	P1

Frequencies

GnomAD3 genomes AF: 0.0905 AC: 13774 AN: 152116 Hom.: 662 Cov.: 32

Gnomad AFR AF: 0.0816

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0743

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.0814

GnomAD4 exome AF: 0.0861 AC: 90377 AN: 1049842 Hom.: 4340 AF XY: 0.0860 AC XY: 46367 AN XY: 539312

Gnomad4 AFR exome AF: 0.0837

Gnomad4 AMR exome AF: 0.0904

Gnomad4 ASJ exome AF: 0.0728

Gnomad4 EAS exome AF: 0.137

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.0811

Gnomad4 OTH exome AF: 0.0855

GnomAD4 genome AF: 0.0905 AC: 13781 AN: 152234 Hom.: 661 Cov.: 32 AF XY: 0.0934 AC XY: 6952 AN XY: 74434

Gnomad4 AFR AF: 0.0815

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.0743

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.0811

Gnomad4 OTH AF: 0.0829

Alfa AF: 0.0217 Hom.: 14

Bravo AF: 0.0899

Asia WGS AF: 0.134 AC: 465 AN: 3478

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

Jun 19, 2018

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	-0.83
CADD	Benign	3.5
DANN	Benign	0.50

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: rs73114428; hg19: chr12-57409381;