rs751487933
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001278716.2(FBXL4):āc.1700T>Cā(p.Leu567Ser) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,954 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. L567L) has been classified as Likely benign.
Frequency
Consequence
NM_001278716.2 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FBXL4 | NM_001278716.2 | c.1700T>C | p.Leu567Ser | missense_variant, splice_region_variant | 9/10 | ENST00000369244.7 | NP_001265645.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FBXL4 | ENST00000369244.7 | c.1700T>C | p.Leu567Ser | missense_variant, splice_region_variant | 9/10 | 1 | NM_001278716.2 | ENSP00000358247.1 | ||
FBXL4 | ENST00000229971.2 | c.1700T>C | p.Leu567Ser | missense_variant, splice_region_variant | 8/9 | 1 | ENSP00000229971.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249788Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135180
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1460954Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726846
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Mitochondrial DNA depletion syndrome 13 Uncertain:1
Uncertain significance, criteria provided, single submitter | reference population | Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine | Aug 10, 2017 | The NM_012160.4:c.1700T>C (NP_036292.2:p.Leu567Ser) [GRCH38: NC_000006.12:g.98875417A>G] variant in FBXL4 gene is interpretated to be a Uncertain Significance - Insufficient 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. Based on this evidence code ClinGen Pathogenicity Calculator (PMID:28081714) suggested that the variant is Uncertain Significance - Insufficient Evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at