12-57016407-G-C

Variant names:

• chr12-57016407-G-C
• rs2291855
• ENST00000300108.7:n.-26C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000300108.7(TAC3):​n.-26C>G variant causes a non coding transcript exon 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 ENST00000300108.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258
• Publications: 5 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -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 rank	MANE	Protein	UniProt
TAC3	NM_013251.4	c.-26C>G		5_prime_UTR_variant	Exon 1 of 7	ENST00000458521.7	NP_037383.1

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 237

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
PhyloP100		-0.26
PromoterAI		-0.0026	Neutral

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: rs2291855; hg19: chr12-57410191;