rs1555973119
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000475.5(NR0B1):c.545_546insCCCA(p.Gly183ProfsTer3) variant causes a frameshift 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 24)
Consequence
NR0B1
NM_000475.5 frameshift
NM_000475.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.769
Publications
0 publications found
Genes affected
NR0B1 (HGNC:7960): (nuclear receptor subfamily 0 group B member 1) This gene encodes a protein that contains a DNA-binding domain. The encoded protein acts as a dominant-negative regulator of transcription which is mediated by the retinoic acid receptor. This protein also functions as an anti-testis gene by acting antagonistically to Sry. Mutations in this gene result in both X-linked congenital adrenal hypoplasia and hypogonadotropic hypogonadism. [provided by RefSeq, Jul 2008]
NR0B1 Gene-Disease associations (from GenCC):
- X-linked adrenal hypoplasia congenitaInheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
- 46,XY sex reversal 2Inheritance: XL Classification: MODERATE Submitted by: Ambry Genetics
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-30308818-C-CTGGG is Pathogenic according to our data. Variant chrX-30308818-C-CTGGG is described in ClinVar as Pathogenic. ClinVar VariationId is 444087.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD3 genomes
Cov.:
24
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome Cov.: 24
GnomAD4 genome
Cov.:
24
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital adrenal hypoplasia, X-linked Pathogenic:1
Sep 27, 2017
Institute of Human Genetics Munich, TUM University Hospital
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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