chr1-61082816-C-T
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_001134673.4(NFIA):c.25C>T(p.Gln9Ter) variant causes a stop gained, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 28)
Consequence
NFIA
NM_001134673.4 stop_gained, splice_region
NM_001134673.4 stop_gained, splice_region
Scores
3
3
1
Splicing: ADA: 0.8380
2
Clinical Significance
Conservation
PhyloP100: 6.19
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 Likely_pathogenic. Variant got 8 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. Fraction of 0.984 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-61082816-C-T is Pathogenic according to our data. Variant chr1-61082816-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 2738411.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NFIA | NM_001134673.4 | c.25C>T | p.Gln9Ter | stop_gained, splice_region_variant | 1/11 | ENST00000403491.8 | NP_001128145.1 | |
NFIA | NM_001145512.2 | c.160C>T | p.Gln54Ter | stop_gained, splice_region_variant | 2/12 | NP_001138984.1 | ||
NFIA | NM_005595.5 | c.25C>T | p.Gln9Ter | stop_gained, splice_region_variant | 1/10 | NP_005586.1 | ||
NFIA | NM_001145511.2 | c.3+5188C>T | intron_variant | NP_001138983.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NFIA | ENST00000403491.8 | c.25C>T | p.Gln9Ter | stop_gained, splice_region_variant | 1/11 | 1 | NM_001134673.4 | ENSP00000384523 | P1 |
Frequencies
GnomAD3 genomes Cov.: 28
GnomAD3 genomes
Cov.:
28
GnomAD4 exome Cov.: 39
GnomAD4 exome
Cov.:
39
GnomAD4 genome Cov.: 28
GnomAD4 genome
Cov.:
28
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 08, 2023 | This sequence change creates a premature translational stop signal (p.Gln9*) in the NFIA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NFIA are known to be pathogenic (PMID: 27081522, 31730271). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NFIA-related conditions. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;A;A;A;A;D;D
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.