chrX-30304676-A-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_000475.5(NR0B1):​c.1316T>G​(p.Ile439Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 23)

Consequence

NR0B1
NM_000475.5 missense

Scores

13
1
3

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.95
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.992
PP5
Variant X-30304676-A-C is Pathogenic according to our data. Variant chrX-30304676-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 10969.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NR0B1NM_000475.5 linkuse as main transcriptc.1316T>G p.Ile439Ser missense_variant 2/2 ENST00000378970.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NR0B1ENST00000378970.5 linkuse as main transcriptc.1316T>G p.Ile439Ser missense_variant 2/21 NM_000475.5 P1P51843-1

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Congenital adrenal hypoplasia, X-linked Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMFeb 01, 2000- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.83
BayesDel_addAF
Pathogenic
0.71
D
BayesDel_noAF
Pathogenic
0.78
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.98
D
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Benign
0.85
T
M_CAP
Pathogenic
0.97
D
MetaRNN
Pathogenic
0.99
D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
3.0
M
MutationTaster
Benign
1.0
A
PrimateAI
Benign
0.46
T
PROVEAN
Pathogenic
-5.3
D
REVEL
Pathogenic
0.97
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.95
MutPred
0.89
Loss of stability (P = 0.0299);
MVP
1.0
MPC
1.8
ClinPred
1.0
D
GERP RS
5.6
Varity_R
0.96
gMVP
0.96

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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.

Other links and lift over

dbSNP: rs104894897; hg19: chrX-30322793; API