14-45159080-TTA-T
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1
The NM_020937.4(FANCM):c.1397-3_1397-2del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,415,016 control chromosomes in the GnomAD database, including 8,448 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.091 ( 764 hom., cov: 30)
Exomes 𝑓: 0.11 ( 7684 hom. )
Consequence
FANCM
NM_020937.4 splice_polypyrimidine_tract, intron
NM_020937.4 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.918
Genes affected
FANCM (HGNC:23168): (FA complementation group M) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group M. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP6
Variant 14-45159080-TTA-T is Benign according to our data. Variant chr14-45159080-TTA-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 261381.We mark this variant Likely_benign, oryginal submissions are: {Benign=5, Uncertain_significance=1}.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCM | NM_020937.4 | c.1397-3_1397-2del | splice_polypyrimidine_tract_variant, intron_variant | ENST00000267430.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCM | ENST00000267430.10 | c.1397-3_1397-2del | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_020937.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0911 AC: 13782AN: 151270Hom.: 763 Cov.: 30
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GnomAD3 exomes AF: 0.177 AC: 23609AN: 133184Hom.: 1461 AF XY: 0.183 AC XY: 13210AN XY: 72324
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GnomAD4 exome AF: 0.112 AC: 141719AN: 1263634Hom.: 7684 AF XY: 0.115 AC XY: 72393AN XY: 629880
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GnomAD4 genome AF: 0.0911 AC: 13789AN: 151382Hom.: 764 Cov.: 30 AF XY: 0.0928 AC XY: 6862AN XY: 73956
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 08, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Premature ovarian failure 15 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Fanconi anemia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Spermatogenic failure 28 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at