rs769919966
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_020937.4(FANCM):c.5026G>A(p.Glu1676Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. E1676E) has been classified as Likely benign.
Frequency
Consequence
NM_020937.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCM | NM_020937.4 | c.5026G>A | p.Glu1676Lys | missense_variant | 20/23 | ENST00000267430.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCM | ENST00000267430.10 | c.5026G>A | p.Glu1676Lys | missense_variant | 20/23 | 1 | NM_020937.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000207 AC: 52AN: 251042Hom.: 0 AF XY: 0.000192 AC XY: 26AN XY: 135696
GnomAD4 exome AF: 0.0000561 AC: 82AN: 1461736Hom.: 0 Cov.: 32 AF XY: 0.0000468 AC XY: 34AN XY: 727182
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74354
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 14, 2021 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with adenomatous polyposis who also carried a truncating APC variant (Kim 2019); This variant is associated with the following publications: (PMID: 27093186, 31269945, 32566746) - |
Hereditary breast ovarian cancer syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Cancer Genomics Group, Japanese Foundation For Cancer Research | May 01, 2019 | - - |
Fanconi anemia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at