12-57016407-G-C

Position:

• chr12-57016407-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013251.4(TAC3):​c.-26C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TAC3 NM_013251.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAC3	NM_013251.4	c.-26C>G		5_prime_UTR_variant	1/7	ENST00000458521.7	NP_037383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAC3	ENST00000458521.7	c.-26C>G		5_prime_UTR_variant	1/7	1	NM_013251.4	ENSP00000404056.2
TAC3	ENST00000300108.7	n.-26C>G		non_coding_transcript_exon_variant	1/9	2		ENSP00000300108.3
TAC3	ENST00000379411.6	n.-26C>G		non_coding_transcript_exon_variant	1/8	2		ENSP00000368721.2
TAC3	ENST00000393867.5	n.-26C>G		non_coding_transcript_exon_variant	1/10	2		ENSP00000377445.1
TAC3	ENST00000300108.7	n.-26C>G		5_prime_UTR_variant	1/9	2		ENSP00000300108.3
TAC3	ENST00000379411.6	n.-26C>G		5_prime_UTR_variant	1/8	2		ENSP00000368721.2
TAC3	ENST00000393867.5	n.-26C>G		5_prime_UTR_variant	1/10	2		ENSP00000377445.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.87
DANN	Benign	0.59

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: rs2291855; hg19: chr12-57410191;