1-155318293-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 8P and 4B. PVS1_ModeratePP3_StrongPP5_ModerateBS2
The NM_002004.4(FDPS):c.684+2T>G variant causes a splice donor change. The variant allele was found at a frequency of 0.000018 in 1,610,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_002004.4 splice_donor
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FDPS | NM_002004.4 | c.684+2T>G | splice_donor_variant | ENST00000368356.9 | |||
RUSC1-AS1 | NR_145424.1 | n.599A>C | non_coding_transcript_exon_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FDPS | ENST00000368356.9 | c.684+2T>G | splice_donor_variant | 2 | NM_002004.4 | ||||
RUSC1-AS1 | ENST00000443642.1 | n.591A>C | non_coding_transcript_exon_variant | 5/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 152066Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000241 AC: 6AN: 248628Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134486
GnomAD4 exome AF: 0.0000158 AC: 23AN: 1458300Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 725528
GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 152066Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74268
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 26, 2019 | This sequence change affects a donor splice site in intron 5 of the FDPS gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs772984674, ExAC 0.009%). This variant has not been reported in the literature in individuals with FDPS-related conditions. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FDPS are known to be pathogenic (PMID: 26202976). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at