rs538555981
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004629.2(FANCG):c.176G>A(p.Gly59Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G59G) has been classified as Likely benign.
Frequency
Consequence
NM_004629.2 missense, splice_region
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 |
---|---|---|---|---|---|---|---|
FANCG | NM_004629.2 | c.176G>A | p.Gly59Glu | missense_variant, splice_region_variant | 3/14 | ENST00000378643.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCG | ENST00000378643.8 | c.176G>A | p.Gly59Glu | missense_variant, splice_region_variant | 3/14 | 1 | NM_004629.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251408Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135892
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727224
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74434
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2021 | This sequence change replaces glycine with glutamic acid at codon 59 of the FANCG protein (p.Gly59Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is present in population databases (rs538555981, ExAC 0.02%). 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: 134363). 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: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at