Genetic Variant NM_001080413.3:c.1864G>T (chr7-144397452-C-A) – 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.1864G>T(p.Asp622Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,384,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D622N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NOBOX
NM_001080413.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.21

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:

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=0.23149735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOBOX	NM_001080413.3 link	c.1864G>T	p.Asp622Tyr	missense_variant	Exon 10 of 10	ENST00000467773.1	NP_001073882.3	O60393-1
NOBOX	NM_001436401.1 link	c.1513G>T	p.Asp505Tyr	missense_variant	Exon 8 of 8		NP_001423330.1
NOBOX	NM_001436402.1 link	c.961G>T	p.Asp321Tyr	missense_variant	Exon 7 of 7		NP_001423331.1
NOBOX	XM_017011742.3 link	c.1768G>T	p.Asp590Tyr	missense_variant	Exon 10 of 10		XP_016867231.1	O60393-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NOBOX	ENST00000467773.1 link	c.1864G>T	p.Asp622Tyr	missense_variant	Exon 10 of 10	5	NM_001080413.3	ENSP00000419457.1	O60393-1
NOBOX	ENST00000483238.5 link	c.1768G>T	p.Asp590Tyr	missense_variant	Exon 10 of 10	5		ENSP00000419565.1	O60393-2
NOBOX	ENST00000645489.1 link	c.1513G>T	p.Asp505Tyr	missense_variant	Exon 8 of 8			ENSP00000496732.1	A0A2R8Y8C8
NOBOX	ENST00000643164.1 link	c.*59G>T		downstream_gene_variant				ENSP00000495343.1	A0A2R8Y683

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1384916

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

683392

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31594

American (AMR)

AF:

0.00

AC:

AN:

35698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.00

AC:

AN:

79234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1078868

Other (OTH)

AF:

0.00

AC:

AN:

57912

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

.;.;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.77

T;T;T

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Uncertain

0.031

MutationAssessor

Benign

1.6

.;.;L

PhyloP100

1.2

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.9

.;D;D

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

.;D;D

Sift4G

Uncertain

0.049

.;D;D

Vest4

0.37, 0.32

MutPred

0.22

.;.;Gain of phosphorylation at D622 (P = 0.0247);

MVP

0.68

MPC

0.19

ClinPred

0.89

GERP RS

1.7

Varity_R

0.086

gMVP

0.26

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over