Variant 7-144400250-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001080413.3(NOBOX):c.907C>G(p.Arg303Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NOBOX
NM_001080413.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.25

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOBOX	NM_001080413.3 linkuse as main transcript	c.907C>G	p.Arg303Gly	missense_variant	5/10	ENST00000467773.1	NP_001073882.3
NOBOX	XM_017011742.3 linkuse as main transcript	c.907C>G	p.Arg303Gly	missense_variant	5/10		XP_016867231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOBOX	ENST00000467773.1 linkuse as main transcript	c.907C>G	p.Arg303Gly	missense_variant	5/10	5	NM_001080413.3	ENSP00000419457		O60393-1
NOBOX	ENST00000483238.5 linkuse as main transcript	c.907C>G	p.Arg303Gly	missense_variant	5/10	5		ENSP00000419565	A2	O60393-2
NOBOX	ENST00000645489.1 linkuse as main transcript	c.652C>G	p.Arg218Gly	missense_variant	3/8			ENSP00000496732	P2
NOBOX	ENST00000643164.1 linkuse as main transcript	c.100C>G	p.Arg34Gly	missense_variant	2/7			ENSP00000495343

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461706

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727134

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.82

.;.;D;.

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.49

T;T;D;T

M_CAP

Uncertain

0.25

MetaRNN

Uncertain

0.61

D;D;D;D

MetaSVM

Uncertain

0.53

MutationAssessor

Benign

1.3

.;L;L;.

MutationTaster

Benign

0.97

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-4.7

.;D;D;.

REVEL

Uncertain

0.56

Sift

Uncertain

0.0010

.;D;D;.

Sift4G

Uncertain

0.0090

.;D;D;.

Polyphen

0.99

.;.;D;.

Vest4

0.60, 0.59

MutPred

0.64

.;Loss of methylation at K301 (P = 0.0497);Loss of methylation at K301 (P = 0.0497);.;

MVP

0.92

MPC

0.19

ClinPred

0.99

GERP RS

3.8

Varity_R

0.48

gMVP

0.28

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over