7-144397518-AG-A
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_001080413.3(NOBOX):c.1797delC(p.Cys600ValfsTer92) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,382,494 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.2e-7 ( 0 hom. )
Consequence
NOBOX
NM_001080413.3 frameshift
NM_001080413.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.572
Publications
0 publications found
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 5Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 6 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.134 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| NOBOX | NM_001080413.3 | c.1797delC | p.Cys600ValfsTer92 | frameshift_variant | Exon 10 of 10 | ENST00000467773.1 | NP_001073882.3 | |
| NOBOX | NM_001436401.1 | c.1446delC | p.Cys483ValfsTer99 | frameshift_variant | Exon 8 of 8 | NP_001423330.1 | ||
| NOBOX | NM_001436402.1 | c.894delC | p.Cys299ValfsTer99 | frameshift_variant | Exon 7 of 7 | NP_001423331.1 | ||
| NOBOX | XM_017011742.3 | c.1701delC | p.Cys568ValfsTer99 | frameshift_variant | Exon 10 of 10 | XP_016867231.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| NOBOX | ENST00000467773.1 | c.1797delC | p.Cys600ValfsTer92 | frameshift_variant | Exon 10 of 10 | 5 | NM_001080413.3 | ENSP00000419457.1 | ||
| NOBOX | ENST00000483238.5 | c.1701delC | p.Cys568ValfsTer92 | frameshift_variant | Exon 10 of 10 | 5 | ENSP00000419565.1 | |||
| NOBOX | ENST00000645489.1 | c.1446delC | p.Cys483ValfsTer92 | frameshift_variant | Exon 8 of 8 | ENSP00000496732.1 | ||||
| NOBOX | ENST00000643164.1 | c.894delC | p.Cys299ValfsTer2 | frameshift_variant | Exon 7 of 7 | ENSP00000495343.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 7.23e-7 AC: 1AN: 1382494Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 681922 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1382494
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
681922
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31520
American (AMR)
AF:
AC:
0
AN:
35556
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25004
East Asian (EAS)
AF:
AC:
0
AN:
35698
South Asian (SAS)
AF:
AC:
0
AN:
79006
European-Finnish (FIN)
AF:
AC:
0
AN:
34930
Middle Eastern (MID)
AF:
AC:
0
AN:
5678
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1077302
Other (OTH)
AF:
AC:
0
AN:
57800
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Premature ovarian failure 5 Uncertain:1
May 17, 2022
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:research
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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