rs587776709
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001079668.3(NKX2-1):c.344delG(p.Gly115AlafsTer10) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NKX2-1
NM_001079668.3 frameshift
NM_001079668.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.69
Publications
5 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]
SFTA3 (HGNC:18387): (surfactant associated 3) Involved in wound healing. Located in cytoplasm and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 14-36519103-GC-G is Pathogenic according to our data. Variant chr14-36519103-GC-G is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 807109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001079668.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NKX2-1 | TSL:1 MANE Select | c.344delG | p.Gly115AlafsTer10 | frameshift | Exon 2 of 3 | ENSP00000346879.6 | P43699-3 | ||
| NKX2-1 | TSL:1 | c.254delG | p.Gly85AlafsTer10 | frameshift | Exon 1 of 2 | ENSP00000429607.2 | P43699-1 | ||
| NKX2-1 | TSL:1 | c.254delG | p.Gly85AlafsTer10 | frameshift | Exon 4 of 5 | ENSP00000429519.4 | P43699-1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000429 AC: 1AN: 233094 AF XY: 0.00000776 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
233094
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1451746Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 722638
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1451746
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
722638
African (AFR)
AF:
AC:
0
AN:
33404
American (AMR)
AF:
AC:
0
AN:
44650
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26070
East Asian (EAS)
AF:
AC:
0
AN:
39650
South Asian (SAS)
AF:
AC:
0
AN:
86092
European-Finnish (FIN)
AF:
AC:
0
AN:
44668
Middle Eastern (MID)
AF:
AC:
0
AN:
5756
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111302
Other (OTH)
AF:
AC:
0
AN:
60154
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic/Likely pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
2
-
-
Brain-lung-thyroid syndrome (2)
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.