1-61082794-G-A
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001134673.4(NFIA):c.3G>A(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 28)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NFIA
NM_001134673.4 start_lost
NM_001134673.4 start_lost
Scores
3
5
9
Clinical Significance
Conservation
PhyloP100: 7.63
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
Start lost variant, no new inframe start found.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-61082794-G-A is Pathogenic according to our data. Variant chr1-61082794-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 2571793.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.3G>A | p.Met1? | start_lost | 1/11 | ENST00000403491.8 | NP_001128145.1 | |
NFIA | NM_005595.5 | c.3G>A | p.Met1? | start_lost | 1/10 | NP_005586.1 | ||
NFIA | NM_001145512.2 | c.138G>A | p.Met46Ile | missense_variant | 2/12 | NP_001138984.1 | ||
NFIA | NM_001145511.2 | c.3+5166G>A | intron_variant | NP_001138983.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NFIA | ENST00000403491.8 | c.3G>A | p.Met1? | start_lost | 1/11 | 1 | NM_001134673.4 | ENSP00000384523 | P1 |
Frequencies
GnomAD3 genomes Cov.: 28
GnomAD3 genomes
Cov.:
28
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1394230Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0AN XY: 687978
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1394230
Hom.:
Cov.:
40
AF XY:
AC XY:
0
AN XY:
687978
Gnomad4 AFR exome
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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 | GeneDx | Jun 28, 2023 | Initiation codon variant in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T
Polyphen
0.0060, 0.011
.;B;B;.;.;.
Vest4
MutPred
0.46
.;Gain of catalytic residue at M1 (P = 0.0018);Gain of catalytic residue at M1 (P = 0.0018);Gain of catalytic residue at M1 (P = 0.0018);Gain of catalytic residue at M1 (P = 0.0018);Gain of catalytic residue at M1 (P = 0.0018);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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
No publications associated with this variant yet.