chr2-74581766-C-CA
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Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 9P and 4B. PVS1PP5BS2
The NM_001321739.2(M1AP):c.676_677insT(p.Trp226LeufsTer4) variant causes a frameshift change. The variant allele was found at a frequency of 0.00333 in 1,614,024 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0023 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0034 ( 6 hom. )
Consequence
M1AP
NM_001321739.2 frameshift
NM_001321739.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.31
Genes affected
M1AP (HGNC:25183): (meiosis 1 associated protein) This gene encodes a protein that is likely to function in progression of meiosis. A similar protein in mouse plays a role in gametogenesis in both sexes. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
Variant 2-74581766-C-CA is Pathogenic according to our data. Variant chr2-74581766-C-CA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 805830.We mark this variant Likely_pathogenic, oryginal submissions are: {Pathogenic=3, Uncertain_significance=1}.
BS2
High Homozygotes in GnomAdExome4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
M1AP | NM_001321739.2 | c.676_677insT | p.Trp226LeufsTer4 | frameshift_variant | 5/11 | ENST00000421985.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
M1AP | ENST00000421985.2 | c.676_677insT | p.Trp226LeufsTer4 | frameshift_variant | 5/11 | 2 | NM_001321739.2 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00228 AC: 347AN: 152162Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00208 AC: 524AN: 251434Hom.: 0 AF XY: 0.00213 AC XY: 290AN XY: 135894
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GnomAD4 exome AF: 0.00344 AC: 5023AN: 1461744Hom.: 6 Cov.: 30 AF XY: 0.00335 AC XY: 2436AN XY: 727182
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GnomAD4 genome AF: 0.00228 AC: 347AN: 152280Hom.: 1 Cov.: 32 AF XY: 0.00196 AC XY: 146AN XY: 74456
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:5Uncertain:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Spermatogenic failure 48 Pathogenic:2Uncertain:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 20, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 18, 2023 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Zotz-Klimas Genetics Lab, MVZ Zotz Klimas | Oct 09, 2023 | - - |
Male infertility with azoospermia or oligozoospermia due to single gene mutation Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Laan Lab, Human Genetics Research Group, University of Tartu | Sep 01, 2023 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2022 | M1AP: PVS1, PP4, PS3:Supporting, PS4:Supporting - |
Non-obstructive azoospermia Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Institute of Reproductive Genetics, University of Münster | May 11, 2020 | - - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at