chr6-98917419-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7
The NM_001278716.2(FBXL4):c.813C>T(p.Leu271=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,612,268 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). Synonymous variant affecting the same amino acid position (i.e. L271L) has been classified as Likely benign.
Frequency
Consequence
NM_001278716.2 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBXL4 | NM_001278716.2 | c.813C>T | p.Leu271= | synonymous_variant | 5/10 | ENST00000369244.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBXL4 | ENST00000369244.7 | c.813C>T | p.Leu271= | synonymous_variant | 5/10 | 1 | NM_001278716.2 | P1 | |
FBXL4 | ENST00000229971.2 | c.813C>T | p.Leu271= | synonymous_variant | 4/9 | 1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000724 AC: 11AN: 152036Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000360 AC: 9AN: 250108Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135100
GnomAD4 exome AF: 0.0000377 AC: 55AN: 1460232Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 726272
GnomAD4 genome AF: 0.0000724 AC: 11AN: 152036Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74266
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.813C>T (NP_036292.2:p.Leu271=) [GRCH38: NC_000006.12:g.98917419G>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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 25, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at