rs374572943
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_022725.4(FANCF):c.350C>T(p.Pro117Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,614,108 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P117T) has been classified as Uncertain significance.
Frequency
Consequence
NM_022725.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCF | NM_022725.4 | c.350C>T | p.Pro117Leu | missense_variant | 1/1 | ENST00000327470.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCF | ENST00000327470.6 | c.350C>T | p.Pro117Leu | missense_variant | 1/1 | NM_022725.4 | P1 | ||
GAS2 | ENST00000648096.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000985 AC: 15AN: 152260Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000275 AC: 69AN: 250602Hom.: 2 AF XY: 0.000339 AC XY: 46AN XY: 135788
GnomAD4 exome AF: 0.000157 AC: 229AN: 1461848Hom.: 3 Cov.: 32 AF XY: 0.000173 AC XY: 126AN XY: 727224
GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152260Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74390
ClinVar
Submissions by phenotype
Fanconi anemia complementation group F Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 26, 2021 | DNA sequence analysis of the FANCF gene demonstrated a sequence change, c.350C>T, in exon 1 that results in an amino acid change, p.Pro117Leu. This sequence change has been described in gnomAD with a frequency of 0.51% in the Ashkenazi Jewish sub-population (dbSNP rs374572943). The p.Pro117Leu change affects a highly 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.Pro117Leu substitution. This sequence change does not appear to have been previously described in patients with FANCF-related disorders. Due to the lack of sufficient evidences, the clinical significance of the p.Pro117Leu change remains unknown at this time. - |
Fanconi anemia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 25, 2023 | - - |
FANCF-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 01, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at