NM_000475.5:c.1169-112_*17delGAAGCTTTGGGTCTTGTTTAATTGGGATGAAACAGAAATGGCTATTTTTAAAAAGCTAGCAAAGGACTCTGTGGTGAGCTGTTTTATAACAAAGAGATTTTTCTCCCTCCAGACGTGCCGGGCCTGCAGTGCGTGAAGTACATTCAGGGACTCCAGTGGGGAACTCAGCAAATACTCAGTGAACACACCAGGATGACGCACCAAGGGCCCCATGACAGATTCATCGAACTTAATAGTACCCTTTTCCTGCTGAGATTCATCAATGCCAATGTCATTGCTGAACTGTTCTTCAGGCCCATCATCGGCACAGTCAGCATGGATGATATGATGCTGGAAATGCTCTGTACAAAGATATAAAGTCATGTGGGCCACACinsTG

Variant names:

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The NM_000475.5(NR0B1):c.1167-112_*17delGAAGCTTTGGGTCTTGTTTAATTGGGATGAAACAGAAATGGCTATTTTTAAAAAGCTAGCAAAGGACTCTGTGGTGAGCTGTTTTATAACAAAGAGATTTTTCTCCCTCCAGACGTGCCGGGCCTGCAGTGCGTGAAGTACATTCAGGGACTCCAGTGGGGAACTCAGCAAATACTCAGTGAACACACCAGGATGACGCACCAAGGGCCCCATGACAGATTCATCGAACTTAATAGTACCCTTTTCCTGCTGAGATTCATCAATGCCAATGTCATTGCTGAACTGTTCTTCAGGCCCATCATCGGCACAGTCAGCATGGATGATATGATGCTGGAAATGCTCTGTACAAAGATATAAAGTCATGTGGGCCACACinsTG variant causes a splice acceptor, splice region, 3 prime UTR, intron 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 (★).

Frequency

Genomes: not found (cov: 23)

Consequence

NR0B1
NM_000475.5 splice_acceptor, splice_region, 3_prime_UTR, intron

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.08

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.4373673 fraction of the gene.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant X-30304562-GTGTGGCCCACATGACTTTATATCTTTGTACAGAGCATTTCCAGCATCATATCATCCATGCTGACTGTGCCGATGATGGGCCTGAAGAACAGTTCAGCAATGACATTGGCATTGATGAATCTCAGCAGGAAAAGGGTACTATTAAGTTCGATGAATCTGTCATGGGGCCCTTGGTGCGTCATCCTGGTGTGTTCACTGAGTATTTGCTGAGTTCCCCACTGGAGTCCCTGAATGTACTTCACGCACTGCAGGCCCGGCACGTCTGGAGGGAGAAAAATCTCTTTGTTATAAAACAGCTCACCACAGAGTCCTTTGCTAGCTTTTTAAAAATAGCCATTTCTGTTTCATCCCAATTAAACAAGACCCAAAGCTTC-CA is Pathogenic according to our data. Variant chrX-30304562-GTGTGGCCCACATGACTTTATATCTTTGTACAGAGCATTTCCAGCATCATATCATCCATGCTGACTGTGCCGATGATGGGCCTGAAGAACAGTTCAGCAATGACATTGGCATTGATGAATCTCAGCAGGAAAAGGGTACTATTAAGTTCGATGAATCTGTCATGGGGCCCTTGGTGCGTCATCCTGGTGTGTTCACTGAGTATTTGCTGAGTTCCCCACTGGAGTCCCTGAATGTACTTCACGCACTGCAGGCCCGGCACGTCTGGAGGGAGAAAAATCTCTTTGTTATAAAACAGCTCACCACAGAGTCCTTTGCTAGCTTTTTAAAAATAGCCATTTCTGTTTCATCCCAATTAAACAAGACCCAAAGCTTC-CA is described in ClinVar as [Pathogenic]. Clinvar id is 444073.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR0B1	NM_000475.5 link	c.1169-112_*17delGAAGCTTTGGGTCTTGTTTAATTGGGATGAAACAGAAATGGCTATTTTTAAAAAGCTAGCAAAGGACTCTGTGGTGAGCTGTTTTATAACAAAGAGATTTTTCTCCCTCCAGACGTGCCGGGCCTGCAGTGCGTGAAGTACATTCAGGGACTCCAGTGGGGAACTCAGCAAATACTCAGTGAACACACCAGGATGACGCACCAAGGGCCCCATGACAGATTCATCGAACTTAATAGTACCCTTTTCCTGCTGAGATTCATCAATGCCAATGTCATTGCTGAACTGTTCTTCAGGCCCATCATCGGCACAGTCAGCATGGATGATATGATGCTGGAAATGCTCTGTACAAAGATATAAAGTCATGTGGGCCACACinsTG	p.Asp390fs	frameshift_variant, stop_lost, splice_region_variant, synonymous_variant	Exon 2 of 2	ENST00000378970.5	NP_000466.2	P51843-1F1D8P4
NR0B1	NM_000475.5 link	c.1167-112_*17delGAAGCTTTGGGTCTTGTTTAATTGGGATGAAACAGAAATGGCTATTTTTAAAAAGCTAGCAAAGGACTCTGTGGTGAGCTGTTTTATAACAAAGAGATTTTTCTCCCTCCAGACGTGCCGGGCCTGCAGTGCGTGAAGTACATTCAGGGACTCCAGTGGGGAACTCAGCAAATACTCAGTGAACACACCAGGATGACGCACCAAGGGCCCCATGACAGATTCATCGAACTTAATAGTACCCTTTTCCTGCTGAGATTCATCAATGCCAATGTCATTGCTGAACTGTTCTTCAGGCCCATCATCGGCACAGTCAGCATGGATGATATGATGCTGGAAATGCTCTGTACAAAGATATAAAGTCATGTGGGCCACACinsTG		splice_acceptor_variant, splice_region_variant, 3_prime_UTR_variant, intron_variant	Exon 2 of 2	ENST00000378970.5	NP_000466.2	P51843-1F1D8P4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR0B1	ENST00000378970.5 link	c.1169-112_*17delGAAGCTTTGGGTCTTGTTTAATTGGGATGAAACAGAAATGGCTATTTTTAAAAAGCTAGCAAAGGACTCTGTGGTGAGCTGTTTTATAACAAAGAGATTTTTCTCCCTCCAGACGTGCCGGGCCTGCAGTGCGTGAAGTACATTCAGGGACTCCAGTGGGGAACTCAGCAAATACTCAGTGAACACACCAGGATGACGCACCAAGGGCCCCATGACAGATTCATCGAACTTAATAGTACCCTTTTCCTGCTGAGATTCATCAATGCCAATGTCATTGCTGAACTGTTCTTCAGGCCCATCATCGGCACAGTCAGCATGGATGATATGATGCTGGAAATGCTCTGTACAAAGATATAAAGTCATGTGGGCCACACinsTG	p.Asp390fs	frameshift_variant, stop_lost, splice_region_variant, synonymous_variant	Exon 2 of 2	1	NM_000475.5	ENSP00000368253.4		P51843-1
NR0B1	ENST00000378970 link	c.1167-112_*17delGAAGCTTTGGGTCTTGTTTAATTGGGATGAAACAGAAATGGCTATTTTTAAAAAGCTAGCAAAGGACTCTGTGGTGAGCTGTTTTATAACAAAGAGATTTTTCTCCCTCCAGACGTGCCGGGCCTGCAGTGCGTGAAGTACATTCAGGGACTCCAGTGGGGAACTCAGCAAATACTCAGTGAACACACCAGGATGACGCACCAAGGGCCCCATGACAGATTCATCGAACTTAATAGTACCCTTTTCCTGCTGAGATTCATCAATGCCAATGTCATTGCTGAACTGTTCTTCAGGCCCATCATCGGCACAGTCAGCATGGATGATATGATGCTGGAAATGCTCTGTACAAAGATATAAAGTCATGTGGGCCACACinsTG		splice_acceptor_variant, splice_region_variant, 3_prime_UTR_variant, intron_variant	Exon 2 of 2	1	NM_000475.5	ENSP00000368253.4		P51843-1

Frequencies

GnomAD3 genomes

Cov.:

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital adrenal hypoplasia, X-linked

Pathogenic:1

Oct 17, 2017

Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.