rs756388446
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_004629.2(FANCG):āc.158T>Gā(p.Leu53Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,455,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. L53L) has been classified as Likely benign.
Frequency
Consequence
NM_004629.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCG | NM_004629.2 | c.158T>G | p.Leu53Arg | missense_variant | 2/14 | ENST00000378643.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCG | ENST00000378643.8 | c.158T>G | p.Leu53Arg | missense_variant | 2/14 | 1 | NM_004629.2 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000839 AC: 2AN: 238482Hom.: 0 AF XY: 0.00000775 AC XY: 1AN XY: 128968
GnomAD4 exome AF: 0.00000275 AC: 4AN: 1455340Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 723482
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Fanconi anemia complementation group G Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 11, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 53 of the FANCG protein (p.Leu53Arg). This variant is present in population databases (rs756388446, gnomAD 0.01%). 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: 456231). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at