NM_001079668.3:c.*209_*210dupTT
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.
The NM_001079668.3(NKX2-1):c.*209_*210dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 874,396 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000014 ( 0 hom., cov: 29)
Exomes 𝑓: 0.00012 ( 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: 0.620
Publications
0 publications found
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 was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| NKX2-1 | NM_001079668.3 | c.*209_*210dupTT | 3_prime_UTR_variant | Exon 3 of 3 | ENST00000354822.7 | NP_001073136.1 | ||
| NKX2-1 | NM_003317.4 | c.*209_*210dupTT | 3_prime_UTR_variant | Exon 2 of 2 | NP_003308.1 | |||
| SFTA3 | NR_161364.1 | n.89+2399_89+2400dupTT | intron_variant | Intron 1 of 4 | ||||
| SFTA3 | NR_161365.1 | n.89+2399_89+2400dupTT | intron_variant | Intron 1 of 4 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| NKX2-1 | ENST00000354822.7 | c.*209_*210dupTT | 3_prime_UTR_variant | Exon 3 of 3 | 1 | NM_001079668.3 | ENSP00000346879.6 | |||
| SFTA3 | ENST00000546983.2 | n.373+1916_373+1917dupTT | intron_variant | Intron 2 of 3 | 4 | ENSP00000449302.2 |
Frequencies
GnomAD3 genomes 0.0000138 AC: 2AN: 144652Hom.: 0 Cov.: 29 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
144652
Hom.:
Cov.:
29
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.000122 AC: 89AN: 729744Hom.: 0 Cov.: 10 AF XY: 0.000110 AC XY: 40AN XY: 362702 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
89
AN:
729744
Hom.:
Cov.:
10
AF XY:
AC XY:
40
AN XY:
362702
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
16550
American (AMR)
AF:
AC:
2
AN:
13470
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
13296
East Asian (EAS)
AF:
AC:
4
AN:
26970
South Asian (SAS)
AF:
AC:
1
AN:
43880
European-Finnish (FIN)
AF:
AC:
1
AN:
25022
Middle Eastern (MID)
AF:
AC:
0
AN:
2342
European-Non Finnish (NFE)
AF:
AC:
75
AN:
554970
Other (OTH)
AF:
AC:
6
AN:
33244
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.288
Heterozygous variant carriers
0
8
15
23
30
38
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000138 AC: 2AN: 144652Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 70188 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
2
AN:
144652
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
70188
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
40270
American (AMR)
AF:
AC:
0
AN:
14118
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3324
East Asian (EAS)
AF:
AC:
0
AN:
5046
South Asian (SAS)
AF:
AC:
0
AN:
4566
European-Finnish (FIN)
AF:
AC:
0
AN:
8996
Middle Eastern (MID)
AF:
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
AC:
2
AN:
65226
Other (OTH)
AF:
AC:
0
AN:
1950
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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