chr5-93585055-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_005654.6(NR2F1):c.32C>T(p.Pro11Leu) variant causes a missense 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NR2F1
NM_005654.6 missense
NM_005654.6 missense
Scores
2
4
8
Clinical Significance
Conservation
PhyloP100: 3.40
Genes affected
NR2F1 (HGNC:7975): (nuclear receptor subfamily 2 group F member 1) The protein encoded by this gene is a nuclear hormone receptor and transcriptional regulator. The encoded protein acts as a homodimer and binds to 5'-AGGTCA-3' repeats. Defects in this gene are a cause of Bosch-Boonstra optic atrophy syndrome (BBOAS). [provided by RefSeq, Apr 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, NR2F1
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR2F1 | NM_005654.6 | c.32C>T | p.Pro11Leu | missense_variant | 1/3 | ENST00000327111.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR2F1 | ENST00000327111.8 | c.32C>T | p.Pro11Leu | missense_variant | 1/3 | 1 | NM_005654.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD3 genomes
?
Cov.:
30
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 890752Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 420746
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
890752
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
420746
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
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Gnomad4 NFE exome
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Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 30
GnomAD4 genome
?
Cov.:
30
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2022 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NR2F1 protein function. ClinVar contains an entry for this variant (Variation ID: 1380872). This variant has not been reported in the literature in individuals affected with NR2F1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 11 of the NR2F1 protein (p.Pro11Leu). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
N;N;.;.
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
Polyphen
P;P;.;.
Vest4
0.23, 0.32
MutPred
Loss of catalytic residue at P11 (P = 0.0093);Loss of catalytic residue at P11 (P = 0.0093);Loss of catalytic residue at P11 (P = 0.0093);Loss of catalytic residue at P11 (P = 0.0093);
MVP
0.83
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.