rs587777432
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001136046.3(ZMYND15):c.1520_1523del(p.Lys507SerfsTer3) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000743 in 1,614,004 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
ZMYND15
NM_001136046.3 frameshift
NM_001136046.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.72
Genes affected
ZMYND15 (HGNC:20997): (zinc finger MYND-type containing 15) This gene encodes a MYND-containing zinc-binding protein with a nuclear localization sequence. A similar gene in mice has been shown to act as a testis-specific transcriptional repressor by recruiting histone deacetylase enzymes to regulate spatiotemporal expression of many haploid genes. This protein may play an important role in spermatogenesis. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jun 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 17-4744208-AAAAC-A is Pathogenic according to our data. Variant chr17-4744208-AAAAC-A is described in ClinVar as [Pathogenic]. Clinvar id is 135663.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-4744208-AAAAC-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZMYND15 | NM_001136046.3 | c.1520_1523del | p.Lys507SerfsTer3 | frameshift_variant | 9/14 | ENST00000433935.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZMYND15 | ENST00000433935.6 | c.1520_1523del | p.Lys507SerfsTer3 | frameshift_variant | 9/14 | 2 | NM_001136046.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152124Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251482Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135914
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GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461880Hom.: 0 AF XY: 0.00000688 AC XY: 5AN XY: 727246
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152124Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4AN XY: 74304
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spermatogenic failure 14 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 01, 2019 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2014 | - - |
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