7-144397520-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080413.3(NOBOX):c.1796C>A(p.Pro599His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,533,932 control chromosomes in the GnomAD database, including 21,039 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1556 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19483 hom. )

Consequence

NOBOX
NM_001080413.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.420

Publications

7 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007170588).

BP6

Variant 7-144397520-G-T is Benign according to our data. Variant chr7-144397520-G-T is described in ClinVar as [Benign]. Clinvar id is 359135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOBOX	NM_001080413.3 link	c.1796C>A	p.Pro599His	missense_variant	Exon 10 of 10	ENST00000467773.1	NP_001073882.3	O60393-1
NOBOX	NM_001436401.1 link	c.1445C>A	p.Pro482His	missense_variant	Exon 8 of 8		NP_001423330.1
NOBOX	NM_001436402.1 link	c.893C>A	p.Pro298His	missense_variant	Exon 7 of 7		NP_001423331.1
NOBOX	XM_017011742.3 link	c.1700C>A	p.Pro567His	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.1796C>A	p.Pro599His	missense_variant	Exon 10 of 10	5	NM_001080413.3	ENSP00000419457.1	O60393-1
NOBOX	ENST00000483238.5 link	c.1700C>A	p.Pro567His	missense_variant	Exon 10 of 10	5		ENSP00000419565.1	O60393-2
NOBOX	ENST00000645489.1 link	c.1445C>A	p.Pro482His	missense_variant	Exon 8 of 8			ENSP00000496732.1	A0A2R8Y8C8
NOBOX	ENST00000643164.1 link	c.893C>A	p.Pro298His	missense_variant	Exon 7 of 7			ENSP00000495343.1	A0A2R8Y683

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19253

AN:

152060

Hom.:

1557

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0521

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.0112

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.159

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.113

GnomAD2 exomes

AF:

0.148

AC:

20191

AN:

136464

AF XY:

0.156

show subpopulations

Gnomad AFR exome

AF:

0.0485

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.00888

Gnomad FIN exome

AF:

0.152

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.162

AC:

223988

AN:

1381754

Hom.:

19483

Cov.:

AF XY:

0.165

AC XY:

112228

AN XY:

681460

show subpopulations

African (AFR)

AF:

0.0479

AC:

1509

AN:

31508

American (AMR)

AF:

0.130

AC:

4615

AN:

35526

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

2772

AN:

24960

East Asian (EAS)

AF:

0.0109

AC:

388

AN:

35690

South Asian (SAS)

AF:

0.225

AC:

17738

AN:

78934

European-Finnish (FIN)

AF:

0.152

AC:

5303

AN:

34916

Middle Eastern (MID)

AF:

0.172

AC:

973

AN:

5666

European-Non Finnish (NFE)

AF:

0.169

AC:

182075

AN:

1076796

Other (OTH)

AF:

0.149

AC:

8615

AN:

57758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

9102

18204

27307

36409

45511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.127

AC:

19263

AN:

152178

Hom.:

1556

Cov.:

AF XY:

0.127

AC XY:

9415

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0521

AC:

2165

AN:

41530

American (AMR)

AF:

0.108

AC:

1655

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

371

AN:

3468

East Asian (EAS)

AF:

0.0112

AC:

AN:

5166

South Asian (SAS)

AF:

0.227

AC:

1093

AN:

4820

European-Finnish (FIN)

AF:

0.159

AC:

1684

AN:

10606

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.170

AC:

11566

AN:

67972

Other (OTH)

AF:

0.115

AC:

242

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

837

1674

2512

3349

4186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.153

Hom.:

5205

Bravo

AF:

0.117

TwinsUK

AF:

0.163

AC:

604

ALSPAC

AF:

0.162

AC:

624

ExAC

AF:

0.144

AC:

3274

Asia WGS

AF:

0.127

AC:

444

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Premature ovarian failure 5

Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.13

.;.;T;.

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.52

T;T;T;T

MetaRNN

Benign

0.0072

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

.;.;L;.

PhyloP100

0.42

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.1

.;D;D;.

REVEL

Benign

0.017

Sift

Benign

0.18

.;T;T;.

Sift4G

Benign

0.32

.;T;T;.

Vest4

0.091, 0.28

MPC

0.041

ClinPred

0.0081

GERP RS

1.4

Varity_R

0.075

gMVP

0.15

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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7-144397520-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over