rs1553149206
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001134673.4(NFIA):c.307dup(p.Cys103LeufsTer16) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
NFIA
NM_001134673.4 frameshift
NM_001134673.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.624
Genes affected
NFIA (HGNC:7784): (nuclear factor I A) This gene encodes a member of the NF1 (nuclear factor 1) family of transcription factors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 1-61088426-G-GT is Pathogenic according to our data. Variant chr1-61088426-G-GT is described in ClinVar as [Pathogenic]. Clinvar id is 520892.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NFIA | NM_001134673.4 | c.307dup | p.Cys103LeufsTer16 | frameshift_variant | 2/11 | ENST00000403491.8 | |
NFIA | NM_001145511.2 | c.283dup | p.Cys95LeufsTer16 | frameshift_variant | 2/11 | ||
NFIA | NM_001145512.2 | c.442dup | p.Cys148LeufsTer16 | frameshift_variant | 3/12 | ||
NFIA | NM_005595.5 | c.307dup | p.Cys103LeufsTer16 | frameshift_variant | 2/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NFIA | ENST00000403491.8 | c.307dup | p.Cys103LeufsTer16 | frameshift_variant | 2/11 | 1 | NM_001134673.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 11, 2016 | - - |
Computational scores
Source:
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Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at