9-124536074-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_033334.4(NR6A1):c.883C>T(p.Leu295Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
NR6A1
NM_033334.4 missense
NM_033334.4 missense
Scores
13
4
2
Clinical Significance
Conservation
PhyloP100: 9.72
Genes affected
NR6A1 (HGNC:7985): (nuclear receptor subfamily 6 group A member 1) This gene encodes an orphan nuclear receptor which is a member of the nuclear hormone receptor family. Its expression pattern suggests that it may be involved in neurogenesis and germ cell development. The protein can homodimerize and bind DNA, but in vivo targets have not been identified. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jun 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.908
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR6A1 | NM_033334.4 | c.883C>T | p.Leu295Phe | missense_variant | 7/10 | ENST00000487099.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR6A1 | ENST00000487099.7 | c.883C>T | p.Leu295Phe | missense_variant | 7/10 | 1 | NM_033334.4 | P4 | |
NR6A1 | ENST00000373584.7 | c.871C>T | p.Leu291Phe | missense_variant | 7/10 | 1 | A1 | ||
NR6A1 | ENST00000416460.6 | c.868C>T | p.Leu290Phe | missense_variant | 7/10 | 1 | A1 | ||
NR6A1 | ENST00000344523.8 | c.880C>T | p.Leu294Phe | missense_variant | 7/10 | 5 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250744Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135500
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461840Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727208
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ExAC
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1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 20, 2021 | The c.883C>T (p.L295F) alteration is located in exon 7 (coding exon 7) of the NR6A1 gene. This alteration results from a C to T substitution at nucleotide position 883, causing the leucine (L) at amino acid position 295 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;T;T
Sift4G
Benign
T;T;T;T
Polyphen
D;.;D;.
Vest4
MutPred
Loss of stability (P = 0.1324);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
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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