Genetic Variant NM_001080413.3:c.262C>A (chr7-144401899-G-T) – 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.262C>A(p.Leu88Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Synonymous variant affecting the same amino acid position (i.e. L88L) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NOBOX
NM_001080413.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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: 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=0.12129623).

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	UniProt
NOBOX	NM_001080413.3	MANE Select	c.262C>A	p.Leu88Met	missense	Exon 3 of 10	NP_001073882.3	O60393-1
NOBOX	NM_001436401.1		c.38-302C>A		intron	N/A	NP_001423330.1	A0A2R8Y8C8
NOBOX	NM_001436402.1		c.38-1587C>A		intron	N/A	NP_001423331.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOBOX	ENST00000467773.1	TSL:5 MANE Select	c.262C>A	p.Leu88Met	missense	Exon 3 of 10	ENSP00000419457.1	O60393-1
NOBOX	ENST00000645489.2		c.38-302C>A		intron	N/A	ENSP00000496732.1
NOBOX	ENST00000643164.2		c.38-1587C>A		intron	N/A	ENSP00000495343.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1459798

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726298

African (AFR)

AF:

0.00

AC:

AN:

33428

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86180

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110214

Other (OTH)

AF:

0.00

AC:

AN:

60302

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.30

CADD

Benign

2.7

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.039

Eigen

Benign

-0.90

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.36

M_CAP

Benign

0.037

MetaRNN

Benign

0.12

MetaSVM

Uncertain

-0.063

MutationAssessor

Benign

0.55

PhyloP100

0.15

PrimateAI

Benign

0.26

PROVEAN

Benign

0.080

REVEL

Benign

0.26

Sift

Benign

0.22

Sift4G

Pathogenic

0.0

Polyphen

0.84

Vest4

0.20

MutPred

0.14

Gain of methylation at K84 (P = 0.0635)

MVP

0.81

MPC

0.022

ClinPred

0.29

GERP RS

-0.10

Varity_R

0.056

gMVP

0.023

Mutation Taster

=99/1

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