chr1-61082792-A-C
Position:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001134673.4(NFIA):c.1A>C(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 28)
Consequence
NFIA
NM_001134673.4 start_lost
NM_001134673.4 start_lost
Scores
2
5
10
Clinical Significance
Conservation
PhyloP100: 7.12
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 10 ACMG points.
PVS1
Start lost variant, no new inframe start found.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NFIA | NM_001134673.4 | c.1A>C | p.Met1? | start_lost | 1/11 | ENST00000403491.8 | NP_001128145.1 | |
NFIA | NM_005595.5 | c.1A>C | p.Met1? | start_lost | 1/10 | NP_005586.1 | ||
NFIA | NM_001145512.2 | c.136A>C | p.Met46Leu | missense_variant | 2/12 | NP_001138984.1 | ||
NFIA | NM_001145511.2 | c.3+5164A>C | intron_variant | NP_001138983.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NFIA | ENST00000403491.8 | c.1A>C | p.Met1? | start_lost | 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: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Brain malformations with or without urinary tract defects Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Mar 06, 2023 | _x000D_ Criteria applied: PVS1_MOD, PS1_MOD, PM2_SUP - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
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
Benign
D;T;T;D;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
0.0060, 0.011
.;B;B;.;.;.
Vest4
MutPred
0.42
.;Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);
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.