rs587777362
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_207341.4(ZP1):c.1169_1176delTTTTCCCA(p.Ile390fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,896 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
ZP1
NM_207341.4 frameshift
NM_207341.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.27
Genes affected
ZP1 (HGNC:13187): (zona pellucida glycoprotein 1) The zona pellucida is an extracellular matrix that surrounds the oocyte and early embryo. It is composed primarily of three or four glycoproteins with various functions during fertilization and preimplantation development. The protein encoded by this gene ensures the structural integrity of the zona pellucida. Mutations in this gene are a cause of oocyte maturation defect and infertility. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 11-60873214-TCCATTTTC-T is Pathogenic according to our data. Variant chr11-60873214-TCCATTTTC-T is described in ClinVar as [Pathogenic]. Clinvar id is 127200.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-60873214-TCCATTTTC-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| ZP1 | NM_207341.4 | c.1169_1176delTTTTCCCA | p.Ile390fs | frameshift_variant | 7/12 | ENST00000278853.10 | NP_997224.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ZP1 | ENST00000278853.10 | c.1169_1176delTTTTCCCA | p.Ile390fs | frameshift_variant | 7/12 | 1 | NM_207341.4 | ENSP00000278853.5 | ||
| ZP1 | ENST00000537203.5 | n.788_795delTTTTCCCA | non_coding_transcript_exon_variant | 3/8 | 1 | |||||
| ZP1 | ENST00000542971.1 | n.410_417delTTTTCCCA | non_coding_transcript_exon_variant | 3/3 | 3 | |||||
| ZP1 | ENST00000543020.1 | n.94_101delTTTTCCCA | non_coding_transcript_exon_variant | 1/4 | 4 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000163 AC: 4AN: 245680Hom.: 0 AF XY: 0.0000302 AC XY: 4AN XY: 132490
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GnomAD4 exome AF: 0.00000275 AC: 4AN: 1455896Hom.: 0 AF XY: 0.00000553 AC XY: 4AN XY: 723838
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Female infertility due to zona pellucida defect Pathogenic:1
| Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 27, 2014 | - - |
Computational scores
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Name
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Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at