14-36519723-AAGAG-AAGAGAGAG
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2
The NM_001079668.3(NKX2-1):c.77+326_77+329dupCTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000579 in 1,450,536 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: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000062 ( 0 hom. )
Consequence
NKX2-1
NM_001079668.3 intron
NM_001079668.3 intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.683
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 Benign. Variant got -8 ACMG points.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0000198 (3/151188) while in subpopulation NFE AF= 0.0000443 (3/67668). AF 95% confidence interval is 0.0000118. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAdExome4 at 81 AD gene.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NKX2-1 | ENST00000354822.7 | c.77+329_77+330insCTCT | intron_variant | Intron 1 of 2 | 1 | NM_001079668.3 | ENSP00000346879.6 | |||
SFTA3 | ENST00000546983.2 | n.-13-354_-13-353insCTCT | intron_variant | Intron 1 of 3 | 4 | ENSP00000449302.2 |
Frequencies
GnomAD3 genomes AF: 0.0000199 AC: 3AN: 151080Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.0000623 AC: 81AN: 1299348Hom.: 0 Cov.: 28 AF XY: 0.0000659 AC XY: 42AN XY: 637198
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GnomAD4 genome AF: 0.0000198 AC: 3AN: 151188Hom.: 0 Cov.: 31 AF XY: 0.0000406 AC XY: 3AN XY: 73844
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at