12-57012465-G-A
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_013251.4(TAC3):c.293-13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000905 in 1,613,950 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000083 ( 1 hom. )
Consequence
TAC3
NM_013251.4 intron
NM_013251.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.69
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 12-57012465-G-A is Benign according to our data. Variant chr12-57012465-G-A is described in ClinVar as [Benign]. Clinvar id is 3627868.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TAC3 | NM_013251.4 | c.293-13C>T | intron_variant | Intron 5 of 6 | ENST00000458521.7 | NP_037383.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TAC3 | ENST00000458521.7 | c.293-13C>T | intron_variant | Intron 5 of 6 | 1 | NM_013251.4 | ENSP00000404056.2 | |||
TAC3 | ENST00000300108.7 | n.293-13C>T | intron_variant | Intron 5 of 8 | 2 | ENSP00000300108.3 | ||||
TAC3 | ENST00000379411.6 | n.239-13C>T | intron_variant | Intron 4 of 7 | 2 | ENSP00000368721.2 | ||||
TAC3 | ENST00000393867.5 | n.*2-13C>T | intron_variant | Intron 6 of 9 | 2 | ENSP00000377445.1 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152100Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000267 AC: 67AN: 251306Hom.: 0 AF XY: 0.000309 AC XY: 42AN XY: 135822
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GnomAD4 exome AF: 0.0000828 AC: 121AN: 1461732Hom.: 1 Cov.: 32 AF XY: 0.000111 AC XY: 81AN XY: 727152
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GnomAD4 genome AF: 0.000164 AC: 25AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74420
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Mar 07, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at