chr7-144397274-G-GC
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_001080413.3(NOBOX):c.2041_2042insG(p.Ala681GlyfsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000361 in 1,384,510 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000036 ( 0 hom. )
Consequence
NOBOX
NM_001080413.3 frameshift
NM_001080413.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.189
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 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 0.508 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 7-144397274-G-GC is Pathogenic according to our data. Variant chr7-144397274-G-GC is described in ClinVar as [Pathogenic]. Clinvar id is 1255994.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOBOX | NM_001080413.3 | c.2041_2042insG | p.Ala681GlyfsTer5 | frameshift_variant | 10/10 | ENST00000467773.1 | |
NOBOX | XM_017011742.3 | c.1945_1946insG | p.Ala649GlyfsTer5 | frameshift_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOBOX | ENST00000467773.1 | c.2041_2042insG | p.Ala681GlyfsTer5 | frameshift_variant | 10/10 | 5 | NM_001080413.3 | ||
NOBOX | ENST00000483238.5 | c.1945_1946insG | p.Ala649GlyfsTer5 | frameshift_variant | 10/10 | 5 | A2 | ||
NOBOX | ENST00000645489.1 | c.1690_1691insG | p.Ala564GlyfsTer5 | frameshift_variant | 8/8 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
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32
GnomAD3 exomes AF: 0.0000141 AC: 2AN: 141736Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 75874
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GnomAD4 exome AF: 0.00000361 AC: 5AN: 1384510Hom.: 0 Cov.: 31 AF XY: 0.00000293 AC XY: 2AN XY: 683126
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Genetic non-acquired premature ovarian failure Pathogenic:1
Pathogenic, no assertion criteria provided | research | Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University | Oct 01, 2019 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at