rs758897077
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_022725.4(FANCF):c.49G>T(p.Val17Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,854 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. V17A) 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.49G>T | p.Val17Phe | missense_variant | 1/1 | ENST00000327470.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCF | ENST00000327470.6 | c.49G>T | p.Val17Phe | missense_variant | 1/1 | NM_022725.4 | P1 | ||
GAS2 | ENST00000528582.5 | c.-72C>A | 5_prime_UTR_variant | 1/6 | 3 | ||||
GAS2 | ENST00000648096.1 | n.254C>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461854Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727228
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2020 | Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals with FANCF-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with phenylalanine at codon 17 of the FANCF protein (p.Val17Phe). The valine residue is highly conserved and there is a small physicochemical difference between valine and phenylalanine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at