chr7-144397415-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001080413.3(NOBOX):c.1901C>T(p.Pro634Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000505 in 1,384,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P634T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

NOBOX
NM_001080413.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.717

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

premature ovarian failure 5
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

NOBOX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07623121).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOBOX	NM_001080413.3 link	c.1901C>T	p.Pro634Leu	missense_variant	Exon 10 of 10	ENST00000467773.1	NP_001073882.3	O60393-1
NOBOX	NM_001436401.1 link	c.1550C>T	p.Pro517Leu	missense_variant	Exon 8 of 8		NP_001423330.1
NOBOX	NM_001436402.1 link	c.998C>T	p.Pro333Leu	missense_variant	Exon 7 of 7		NP_001423331.1
NOBOX	XM_017011742.3 link	c.1805C>T	p.Pro602Leu	missense_variant	Exon 10 of 10		XP_016867231.1	O60393-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NOBOX	ENST00000467773.1 link	c.1901C>T	p.Pro634Leu	missense_variant	Exon 10 of 10	5	NM_001080413.3	ENSP00000419457.1	O60393-1
NOBOX	ENST00000483238.5 link	c.1805C>T	p.Pro602Leu	missense_variant	Exon 10 of 10	5		ENSP00000419565.1	O60393-2
NOBOX	ENST00000645489.1 link	c.1550C>T	p.Pro517Leu	missense_variant	Exon 8 of 8			ENSP00000496732.1	A0A2R8Y8C8
NOBOX	ENST00000643164.1 link	c.*96C>T		downstream_gene_variant				ENSP00000495343.1	A0A2R8Y683

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

140284

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000505

AC:

AN:

1384938

Hom.:

Cov.:

AF XY:

0.00000439

AC XY:

AN XY:

683400

show subpopulations

African (AFR)

AF:

0.0000950

AC:

AN:

31594

American (AMR)

AF:

0.00

AC:

AN:

35698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.00

AC:

AN:

79234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35000

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078886

Other (OTH)

AF:

0.0000173

AC:

AN:

57914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

NOBOX: PM2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.041

.;.;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.54

T;T;T

M_CAP

Benign

0.079

MetaRNN

Benign

0.076

T;T;T

MetaSVM

Benign

-0.31

MutationAssessor

Benign

0.0

.;.;N

PhyloP100

0.72

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.060

.;N;N

REVEL

Benign

0.14

Sift

Benign

0.047

.;D;T

Sift4G

Benign

0.088

.;T;T

Vest4

0.093, 0.080

MutPred

0.20

.;.;Loss of glycosylation at T631 (P = 0.0964);

MVP

0.63

MPC

0.023

ClinPred

0.080

GERP RS

2.6

Varity_R

0.028

gMVP

0.11

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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chr7-144397415-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over