rs201153812
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_004629.2(FANCG):c.421C>T(p.Arg141Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,614,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 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. R141H) has been classified as Uncertain significance.
Frequency
Consequence
NM_004629.2 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 |
---|---|---|---|---|---|---|---|
FANCG | NM_004629.2 | c.421C>T | p.Arg141Cys | missense_variant | 4/14 | ENST00000378643.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCG | ENST00000378643.8 | c.421C>T | p.Arg141Cys | missense_variant | 4/14 | 1 | NM_004629.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000167 AC: 42AN: 251220Hom.: 0 AF XY: 0.000147 AC XY: 20AN XY: 135840
GnomAD4 exome AF: 0.0000465 AC: 68AN: 1461848Hom.: 0 Cov.: 32 AF XY: 0.0000481 AC XY: 35AN XY: 727226
GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74476
ClinVar
Submissions by phenotype
Fanconi anemia complementation group G Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 13, 2020 | - - |
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 141 of the FANCG protein (p.Arg141Cys). This variant is present in population databases (rs201153812, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with FANCG-related conditions. ClinVar contains an entry for this variant (Variation ID: 239967). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at