rs104894889

chrX-30308660-C-AchrX-30308660-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000475.5(NR0B1):c.704G>T(p.Trp235Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: NR0B1 NM_000475.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1757561).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR0B1	NM_000475.5	c.704G>T	p.Trp235Leu	missense_variant	1/2	ENST00000378970.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR0B1	ENST00000378970.5	c.704G>T	p.Trp235Leu	missense_variant	1/2	1	NM_000475.5	P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
Cadd	Benign	13
Dann	Benign	0.96
DEOGEN2	Benign	0.26	T
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.47	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.18	T
MetaSVM	Uncertain	0.44	D
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	0.98	N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.43
Sift	Benign	0.077	T
Sift4G	Benign	0.14	T
Polyphen		0.13	B
Vest4		0.30
MutPred		0.37		Loss of loop (P = 0.0288);
MVP		0.85
MPC		1.0
ClinPred		0.45	T
GERP RS		3.5
Varity_R		0.40
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-30326777;