Variant 7-144397409-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001080413.3(NOBOX):c.1907C>A(p.Ala636Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,537,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

NOBOX
NM_001080413.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.374

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.088850975).

BS2

High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOBOX	NM_001080413.3 linkuse as main transcript	c.1907C>A	p.Ala636Asp	missense_variant	10/10	ENST00000467773.1	NP_001073882.3	O60393-1
NOBOX	XM_017011742.3 linkuse as main transcript	c.1811C>A	p.Ala604Asp	missense_variant	10/10		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.1907C>A	p.Ala636Asp	missense_variant	10/10	5	NM_001080413.3	ENSP00000419457.1	O60393-1
NOBOX	ENST00000483238.5 linkuse as main transcript	c.1811C>A	p.Ala604Asp	missense_variant	10/10	5		ENSP00000419565.1	O60393-2
NOBOX	ENST00000645489.1 linkuse as main transcript	c.1556C>A	p.Ala519Asp	missense_variant	8/8			ENSP00000496732.1	A0A2R8Y8C8

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000142

AC:

AN:

140466

Hom.:

AF XY:

0.00

AC XY:

AN XY:

75308

show subpopulations

Gnomad AFR exome

AF:

0.000264

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000116

AC:

AN:

1384938

Hom.:

Cov.:

AF XY:

0.0000132

AC XY:

AN XY:

683400

show subpopulations

Gnomad4 AFR exome

AF:

0.000222

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:

0.00000649

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.000171

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.000627

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000132

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 11, 2024

The c.1907C>A (p.A636D) alteration is located in exon 10 (coding exon 10) of the NOBOX gene. This alteration results from a C to A substitution at nucleotide position 1907, causing the alanine (A) at amino acid position 636 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.15

.;.;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.33

T;T;T

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.089

T;T;T

MetaSVM

Uncertain

0.055

MutationAssessor

Benign

1.8

.;.;L

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.1

.;N;N

REVEL

Benign

0.27

Sift

Uncertain

0.0020

.;D;D

Sift4G

Uncertain

0.042

.;D;D

Vest4

0.27, 0.21

MutPred

0.073

.;.;Loss of glycosylation at P641 (P = 0.1015);

MVP

0.65

MPC

0.19

ClinPred

0.16

GERP RS

1.3

Varity_R

0.10

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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