NM_001080413.3:c.262C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001080413.3(NOBOX):c.262C>T(p.Leu88Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,609,278 control chromosomes in the GnomAD database, including 290,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 28882 hom., cov: 31)

Exomes 𝑓: 0.59 ( 262007 hom. )

Consequence

NOBOX
NM_001080413.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.146

Publications

24 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 7-144401899-G-A is Benign according to our data. Variant chr7-144401899-G-A is described in ClinVar as [Benign]. Clinvar id is 359152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.146 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOBOX	NM_001080413.3 link	c.262C>T	p.Leu88Leu	synonymous_variant	Exon 3 of 10	ENST00000467773.1	NP_001073882.3	O60393-1
NOBOX	XM_017011742.3 link	c.262C>T	p.Leu88Leu	synonymous_variant	Exon 3 of 10		XP_016867231.1	O60393-2
NOBOX	NM_001436401.1 link	c.38-302C>T		intron_variant	Intron 1 of 7		NP_001423330.1
NOBOX	NM_001436402.1 link	c.38-1587C>T		intron_variant	Intron 1 of 6		NP_001423331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NOBOX	ENST00000467773.1 link	c.262C>T	p.Leu88Leu	synonymous_variant	Exon 3 of 10	5	NM_001080413.3	ENSP00000419457.1	O60393-1
NOBOX	ENST00000483238.5 link	c.262C>T	p.Leu88Leu	synonymous_variant	Exon 3 of 10	5		ENSP00000419565.1	O60393-2
NOBOX	ENST00000645489.1 link	c.38-302C>T		intron_variant	Intron 1 of 7			ENSP00000496732.1	A0A2R8Y8C8
NOBOX	ENST00000643164.1 link	c.38-1587C>T		intron_variant	Intron 1 of 6			ENSP00000495343.1	A0A2R8Y683

Frequencies

GnomAD3 genomes

AF:

0.612

AC:

92907

AN:

151814

Hom.:

28852

Cov.:

show subpopulations

Gnomad AFR

AF:

0.645

Gnomad AMI

AF:

0.656

Gnomad AMR

AF:

0.620

Gnomad ASJ

AF:

0.606

Gnomad EAS

AF:

0.829

Gnomad SAS

AF:

0.831

Gnomad FIN

AF:

0.538

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.619

GnomAD2 exomes

AF:

0.632

AC:

157122

AN:

248510

AF XY:

0.638

show subpopulations

Gnomad AFR exome

AF:

0.651

Gnomad AMR exome

AF:

0.651

Gnomad ASJ exome

AF:

0.599

Gnomad EAS exome

AF:

0.822

Gnomad FIN exome

AF:

0.533

Gnomad NFE exome

AF:

0.571

Gnomad OTH exome

AF:

0.598

GnomAD4 exome

AF:

0.595

AC:

866739

AN:

1457346

Hom.:

262007

Cov.:

AF XY:

0.602

AC XY:

436375

AN XY:

725156

show subpopulations

African (AFR)

AF:

0.646

AC:

21562

AN:

33360

American (AMR)

AF:

0.646

AC:

28864

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.603

AC:

15730

AN:

26084

East Asian (EAS)

AF:

0.788

AC:

31258

AN:

39680

South Asian (SAS)

AF:

0.799

AC:

68756

AN:

86094

European-Finnish (FIN)

AF:

0.529

AC:

28212

AN:

53380

Middle Eastern (MID)

AF:

0.666

AC:

3834

AN:

5760

European-Non Finnish (NFE)

AF:

0.570

AC:

631425

AN:

1108090

Other (OTH)

AF:

0.616

AC:

37098

AN:

60214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

15274

30548

45822

61096

76370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.612

AC:

92989

AN:

151932

Hom.:

28882

Cov.:

AF XY:

0.617

AC XY:

45817

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.644

AC:

26681

AN:

41402

American (AMR)

AF:

0.620

AC:

9471

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.606

AC:

2099

AN:

3464

East Asian (EAS)

AF:

0.829

AC:

4267

AN:

5148

South Asian (SAS)

AF:

0.832

AC:

4003

AN:

4810

European-Finnish (FIN)

AF:

0.538

AC:

5672

AN:

10544

Middle Eastern (MID)

AF:

0.711

AC:

209

AN:

294

European-Non Finnish (NFE)

AF:

0.569

AC:

38673

AN:

67966

Other (OTH)

AF:

0.624

AC:

1316

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1825

3650

5474

7299

9124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.579

Hom.:

36593

Bravo

AF:

0.615

Asia WGS

AF:

0.812

AC:

2821

AN:

3478

EpiCase

AF:

0.583

EpiControl

AF:

0.586

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

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

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

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.4

(source)

DANN

Benign

0.53

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism (auto)

(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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NM_001080413.3:c.262C>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