7-144398507-A-G

Position:

chr7-144398507-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080413.3(NOBOX):c.1549T>C(p.Phe517Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,535,894 control chromosomes in the GnomAD database, including 258,161 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27119 hom., cov: 30)

Exomes 𝑓: 0.57 ( 231042 hom. )

Consequence

NOBOX
NM_001080413.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.77

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.9674754E-6).

BP6

Variant 7-144398507-A-G is Benign according to our data. Variant chr7-144398507-A-G is described in ClinVar as [Benign]. Clinvar id is 286525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-144398507-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOBOX	NM_001080413.3 linkuse as main transcript	c.1549T>C	p.Phe517Leu	missense_variant	9/10	ENST00000467773.1	NP_001073882.3	O60393-1
NOBOX	XM_017011742.3 linkuse as main transcript	c.1453T>C	p.Phe485Leu	missense_variant	9/10		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.1549T>C	p.Phe517Leu	missense_variant	9/10	5	NM_001080413.3	ENSP00000419457.1	O60393-1
NOBOX	ENST00000483238.5 linkuse as main transcript	c.1453T>C	p.Phe485Leu	missense_variant	9/10	5		ENSP00000419565.1	O60393-2
NOBOX	ENST00000645489.1 linkuse as main transcript	c.1198T>C	p.Phe400Leu	missense_variant	7/8			ENSP00000496732.1	A0A2R8Y8C8
NOBOX	ENST00000643164.1 linkuse as main transcript	c.646T>C	p.Phe216Leu	missense_variant	6/7			ENSP00000495343.1	A0A2R8Y683

Frequencies

GnomAD3 genomes

AF:

0.593

AC:

89838

AN:

151604

Hom.:

27090

Cov.:

show subpopulations

Gnomad AFR

AF:

0.627

Gnomad AMI

AF:

0.650

Gnomad AMR

AF:

0.607

Gnomad ASJ

AF:

0.586

Gnomad EAS

AF:

0.829

Gnomad SAS

AF:

0.831

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.706

Gnomad NFE

AF:

0.545

Gnomad OTH

AF:

0.607

GnomAD3 exomes

AF:

0.634

AC:

88686

AN:

139948

Hom.:

29003

AF XY:

0.644

AC XY:

48303

AN XY:

75032

show subpopulations

Gnomad AFR exome

AF:

0.636

Gnomad AMR exome

AF:

0.639

Gnomad ASJ exome

AF:

0.580

Gnomad EAS exome

AF:

0.822

Gnomad SAS exome

AF:

0.798

Gnomad FIN exome

AF:

0.505

Gnomad NFE exome

AF:

0.553

Gnomad OTH exome

AF:

0.591

GnomAD4 exome

AF:

0.573

AC:

792533

AN:

1384172

Hom.:

231042

Cov.:

AF XY:

0.580

AC XY:

396440

AN XY:

683020

show subpopulations

Gnomad4 AFR exome

AF:

0.630

Gnomad4 AMR exome

AF:

0.633

Gnomad4 ASJ exome

AF:

0.582

Gnomad4 EAS exome

AF:

0.786

Gnomad4 SAS exome

AF:

0.797

Gnomad4 FIN exome

AF:

0.501

Gnomad4 NFE exome

AF:

0.546

Gnomad4 OTH exome

AF:

0.599

GnomAD4 genome

AF:

0.593

AC:

89915

AN:

151722

Hom.:

27119

Cov.:

AF XY:

0.598

AC XY:

44319

AN XY:

74130

show subpopulations

Gnomad4 AFR

AF:

0.627

Gnomad4 AMR

AF:

0.607

Gnomad4 ASJ

AF:

0.586

Gnomad4 EAS

AF:

0.829

Gnomad4 SAS

AF:

0.832

Gnomad4 FIN

AF:

0.512

Gnomad4 NFE

AF:

0.545

Gnomad4 OTH

AF:

0.612

Alfa

AF:

0.557

Hom.:

14145

Bravo

AF:

0.596

TwinsUK

AF:

0.557

AC:

2067

ALSPAC

AF:

0.526

AC:

2027

ExAC

AF:

0.554

AC:

16006

Asia WGS

AF:

0.809

AC:

2812

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Premature ovarian failure 5

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Feb 25, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

.;.;T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.48

T;T;T;T

MetaRNN

Benign

0.0000050

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

.;.;M;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-2.0

.;N;N;.

REVEL

Benign

0.022

Sift

Uncertain

0.0010

.;D;D;.

Sift4G

Benign

0.13

.;T;T;.

Vest4

0.068, 0.22

MutPred

0.26

.;.;Gain of phosphorylation at S520 (P = 0.1252);.;

MPC

0.096

ClinPred

0.030

GERP RS

3.0

Varity_R

0.18

gMVP

0.21

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over