16-70463239-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_145059.3(FCSK):c.49C>T(p.Gln17*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000223 in 1,613,930 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 (★★).
Frequency
Consequence
NM_145059.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000601 AC: 15AN: 249538Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135396
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461800Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 727206
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74296
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: FCSK c.49C>T (p.Gln17X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, however the molecular mechanism of disease attributed to FCSK is currently unknown. The variant allele was found at a frequency of 2.2e-05 in 1613930 control chromosomes. To our knowledge, no occurrence of c.49C>T in individuals affected with Congenital Disorder Of Glycosylation With Defective Fucosylation and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 3000867). Based on the evidence outlined above, the variant was classified as uncertain significance. -
not provided Uncertain:1
This sequence change creates a premature translational stop signal (p.Gln17*) in the FUK gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in FUK cause disease. This variant is present in population databases (rs753175029, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with FUK-related conditions. 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