chr11-22625510-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_022725.4(FANCF):c.301C>T(p.Arg101Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R101P) has been classified as Uncertain significance.
Frequency
Consequence
NM_022725.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCF | NM_022725.4 | c.301C>T | p.Arg101Trp | missense_variant | 1/1 | ENST00000327470.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCF | ENST00000327470.6 | c.301C>T | p.Arg101Trp | missense_variant | 1/1 | NM_022725.4 | P1 | ||
GAS2 | ENST00000648096.1 | n.2G>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250846Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135758
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461844Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727224
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 01, 2021 | DNA sequence analysis of the FANCF gene demonstrated a sequence change, c.301C>T, in exon 1 that results in an amino acid change, p.Arg101Trp. This sequence change has been described in the gnomAD database in one heterozygous individual which corresponds to a population frequency of 0.0004% (dbSNP rs760571335). The p.Arg101Trp change affects a moderately conserved amino acid residue located in a domain of the FANCF protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Arg101Trp substitution. This sequence change does not appear to have been previously described in individuals with FANCF-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Arg101Trp change remains unknown at this time. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at