chr19-13024680-C-CGT
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 8P and 4B. PVS1BS2
The NM_001378405.1(NFIX):c.46_47dupTG(p.Trp16CysfsTer58) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000391 in 1,535,636 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000036 ( 0 hom. )
Consequence
NFIX
NM_001378405.1 frameshift
NM_001378405.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.11
Genes affected
NFIX (HGNC:7788): (nuclear factor I X) The protein encoded by this gene is a transcription factor that binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3 in viral and cellular promoters. The encoded protein can also stimulate adenovirus replication in vitro. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 52 pathogenic variants in the truncated region.
BS2
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| NFIX | NM_001365902.3 | c.28-331_28-330dupTG | intron_variant | Intron 1 of 10 | ENST00000592199.6 | NP_001352831.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.00000659 AC: 1AN: 151756Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000361 AC: 5AN: 1383880Hom.: 0 Cov.: 32 AF XY: 0.00000293 AC XY: 2AN XY: 682876
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GnomAD4 genome 0.00000659 AC: 1AN: 151756Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74088
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Marshall-Smith syndrome;C3553660:Malan overgrowth syndrome Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 03, 2023 | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. This variant has not been reported in the literature in individuals affected with NFIX-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 1 of the NFIX gene. It does not directly change the encoded amino acid sequence of the NFIX protein. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.