chr6-98875551-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_ModerateBP6BP7BS1
The NM_001278716.2(FBXL4):c.1566C>T(p.Thr522Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001278716.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FBXL4 | ENST00000369244.7 | c.1566C>T | p.Thr522Thr | synonymous_variant | Exon 9 of 10 | 1 | NM_001278716.2 | ENSP00000358247.1 | ||
FBXL4 | ENST00000229971.2 | c.1566C>T | p.Thr522Thr | synonymous_variant | Exon 8 of 9 | 1 | ENSP00000229971.1 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152116Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000239 AC: 60AN: 250998Hom.: 0 AF XY: 0.000258 AC XY: 35AN XY: 135626
GnomAD4 exome AF: 0.000123 AC: 180AN: 1461828Hom.: 0 Cov.: 31 AF XY: 0.000168 AC XY: 122AN XY: 727210
GnomAD4 genome AF: 0.000112 AC: 17AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74438
ClinVar
Submissions by phenotype
not provided Benign:2
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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Mitochondrial DNA depletion syndrome 13 Uncertain:1
The NM_012160.4:c.1566C>T (NP_036292.2:p.Thr522=) [GRCH38: NC_000006.12:g.98875551G>A] variant in FBXL4 gene is interpretated to be a Uncertain Significance - Conflicting Evidence based on ACMG guidelines (PMID: 25741868). This variant meets one or more of the following evidence codes reported in the ACMG-guideline. PM2:This variant is absent in key population databases. BP4:Computational evidence/predictors indicate no impact on the FBXL4 structure, function, or protein-protein interaction. BP7:The variant is silent with non predicted splice impact. Based on this evidence code ClinGen Pathogenicity Calculator (PMID:28081714) suggested that the variant is Uncertain Significance - Conflicting Evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at