14-36517091-A-AGGGTTGG
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001079668.3(NKX2-1):c.*186_*187insCCAACCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000114 in 876,716 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 28)
Exomes 𝑓: 0.0000011 ( 0 hom. )
Consequence
NKX2-1
NM_001079668.3 3_prime_UTR
NM_001079668.3 3_prime_UTR
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.0890
Genes affected
NKX2-1 (HGNC:11825): (NK2 homeobox 1) This gene encodes a protein initially identified as a thyroid-specific transcription factor. The encoded protein binds to the thyroglobulin promoter and regulates the expression of thyroid-specific genes but has also been shown to regulate the expression of genes involved in morphogenesis. Mutations and deletions in this gene are associated with benign hereditary chorea, choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress, and may be associated with thyroid cancer. Multiple transcript variants encoding different isoforms have been found for this gene. This gene shares the symbol/alias 'TTF1' with another gene, transcription termination factor 1, which plays a role in ribosomal gene transcription. [provided by RefSeq, Feb 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NKX2-1 | NM_001079668.3 | c.*186_*187insCCAACCC | 3_prime_UTR_variant | Exon 3 of 3 | ENST00000354822.7 | NP_001073136.1 | ||
NKX2-1 | NM_003317.4 | c.*186_*187insCCAACCC | 3_prime_UTR_variant | Exon 2 of 2 | NP_003308.1 | |||
SFTA3 | NR_161364.1 | n.89+2376_89+2377insCCAACCC | intron_variant | Intron 1 of 4 | ||||
SFTA3 | NR_161365.1 | n.89+2376_89+2377insCCAACCC | intron_variant | Intron 1 of 4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NKX2-1 | ENST00000354822 | c.*186_*187insCCAACCC | 3_prime_UTR_variant | Exon 3 of 3 | 1 | NM_001079668.3 | ENSP00000346879.6 | |||
SFTA3 | ENST00000546983.2 | n.373+1893_373+1894insCCAACCC | intron_variant | Intron 2 of 3 | 4 | ENSP00000449302.2 |
Frequencies
GnomAD3 genomes Cov.: 28
GnomAD3 genomes
Cov.:
28
GnomAD4 exome AF: 0.00000114 AC: 1AN: 876716Hom.: 0 Cov.: 12 AF XY: 0.00000232 AC XY: 1AN XY: 430776
GnomAD4 exome
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AN:
876716
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12
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AN XY:
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GnomAD4 genome Cov.: 28
GnomAD4 genome
Cov.:
28
ClinVar
Not reported inComputational scores
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Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at