Genetic Variant NOBOX:p.Arg117Gly (chr7-144401541-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080413.3(NOBOX):c.349C>G(p.Arg117Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000734 in 1,362,778 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R117W) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

NOBOX
NM_001080413.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.28

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.099730045).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080413.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NOBOX	NM_001080413.3	MANE Select	c.349C>G	p.Arg117Gly	missense	Exon 4 of 10	NP_001073882.3
NOBOX	NM_001436401.1		c.94C>G	p.Arg32Gly	missense	Exon 2 of 8	NP_001423330.1
NOBOX	NM_001436402.1		c.38-1229C>G		intron	N/A	NP_001423331.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NOBOX	ENST00000467773.1	TSL:5 MANE Select	c.349C>G	p.Arg117Gly	missense	Exon 4 of 10	ENSP00000419457.1
NOBOX	ENST00000483238.5	TSL:5	c.349C>G	p.Arg117Gly	missense	Exon 4 of 10	ENSP00000419565.1
NOBOX	ENST00000645489.1		c.94C>G	p.Arg32Gly	missense	Exon 2 of 8	ENSP00000496732.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.34e-7

AC:

AN:

1362778

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

667760

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30234

American (AMR)

AF:

0.00

AC:

AN:

28908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19884

East Asian (EAS)

AF:

0.00

AC:

AN:

38970

South Asian (SAS)

AF:

0.00

AC:

AN:

68236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46114

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1068928

Other (OTH)

AF:

0.0000178

AC:

AN:

56196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.13

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.47

M_CAP

Benign

0.069

MetaRNN

Benign

0.10

MetaSVM

Uncertain

-0.12

MutationAssessor

Benign

0.34

PhyloP100

1.3

PrimateAI

Benign

0.19

PROVEAN

Benign

-1.8

REVEL

Benign

0.19

Sift

Uncertain

0.0030

Sift4G

Benign

0.075

Polyphen

0.093

Vest4

0.30

MutPred

0.18

Gain of glycosylation at S119 (P = 0.0876)

MVP

0.78

MPC

0.027

ClinPred

0.15

GERP RS

3.5

Varity_R

0.093

gMVP

0.051

Mutation Taster

=92/8

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over