Variant 7-144397469-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001080413.3(NOBOX):c.1847G>A(p.Gly616Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,384,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

NOBOX
NM_001080413.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.29

Variant links:

Genes affected

NOBOX (HGNC:22448): (NOBOX oogenesis homeobox) This homeobox gene encodes a transcription factor that is thought to play a role in oogenesis. In mice, it is essential for folliculogenesis and regulation of oocyte-specific genes. Defects in this gene result in premature ovarian failure type 5.[provided by RefSeq, May 2011]

NOBOX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29366833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOBOX	NM_001080413.3 linkuse as main transcript	c.1847G>A	p.Gly616Glu	missense_variant	10/10	ENST00000467773.1	NP_001073882.3	O60393-1
NOBOX	XM_017011742.3 linkuse as main transcript	c.1751G>A	p.Gly584Glu	missense_variant	10/10		XP_016867231.1	O60393-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NOBOX	ENST00000467773.1 linkuse as main transcript	c.1847G>A	p.Gly616Glu	missense_variant	10/10	5	NM_001080413.3	ENSP00000419457.1	O60393-1
NOBOX	ENST00000483238.5 linkuse as main transcript	c.1751G>A	p.Gly584Glu	missense_variant	10/10	5		ENSP00000419565.1	O60393-2
NOBOX	ENST00000645489.1 linkuse as main transcript	c.1496G>A	p.Gly499Glu	missense_variant	8/8			ENSP00000496732.1	A0A2R8Y8C8
NOBOX	ENST00000643164.1 linkuse as main transcript	c.*42G>A		downstream_gene_variant				ENSP00000495343.1	A0A2R8Y683

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.22e-7

AC:

AN:

1384890

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

683370

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

The c.1847G>A (p.G616E) alteration is located in exon 10 (coding exon 10) of the NOBOX gene. This alteration results from a G to A substitution at nucleotide position 1847, causing the glycine (G) at amino acid position 616 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

.;.;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.78

T;T;T

M_CAP

Pathogenic

0.59

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Uncertain

0.72

MutationAssessor

Uncertain

2.0

.;.;M

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.4

.;D;D

REVEL

Uncertain

0.39

Sift

Uncertain

0.0020

.;D;D

Sift4G

Uncertain

0.060

.;T;T

Vest4

0.64, 0.45

MutPred

0.21

.;.;Gain of solvent accessibility (P = 0.0374);

MVP

0.83

MPC

0.20

ClinPred

0.89

GERP RS

4.5

Varity_R

0.28

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over