12-57012866-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4
The NM_013251.4(TAC3):āc.248A>Gā(p.His83Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000326 in 1,614,160 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_013251.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TAC3 | NM_013251.4 | c.248A>G | p.His83Arg | missense_variant | Exon 5 of 7 | ENST00000458521.7 | NP_037383.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TAC3 | ENST00000458521.7 | c.248A>G | p.His83Arg | missense_variant | Exon 5 of 7 | 1 | NM_013251.4 | ENSP00000404056.2 | ||
TAC3 | ENST00000300108.7 | n.248A>G | non_coding_transcript_exon_variant | Exon 5 of 9 | 2 | ENSP00000300108.3 | ||||
TAC3 | ENST00000393867.5 | n.248A>G | non_coding_transcript_exon_variant | Exon 5 of 10 | 2 | ENSP00000377445.1 | ||||
TAC3 | ENST00000379411.6 | n.239-414A>G | intron_variant | Intron 4 of 7 | 2 | ENSP00000368721.2 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152174Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000155 AC: 39AN: 251452Hom.: 0 AF XY: 0.000191 AC XY: 26AN XY: 135890
GnomAD4 exome AF: 0.000347 AC: 507AN: 1461868Hom.: 0 Cov.: 32 AF XY: 0.000319 AC XY: 232AN XY: 727236
GnomAD4 genome AF: 0.000125 AC: 19AN: 152292Hom.: 1 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74478
ClinVar
Submissions by phenotype
not provided Uncertain:2
This sequence change replaces histidine with arginine at codon 83 of the TAC3 protein (p.His83Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is present in population databases (rs143862988, ExAC 0.05%). This missense change has been observed in individual(s) with clinical features of TAC3-related conditions (PMID: 25636053, 29419413). ClinVar contains an entry for this variant (Variation ID: 180150). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
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Delayed puberty Pathogenic:1
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Infertility disorder Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at