rs778493200
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000553.6(WRN):c.725-3del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,609,342 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000553.6 splice_region, splice_polypyrimidine_tract, intron
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 | UniProt |
---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.725-3del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.725-3del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000553.6 | P1 | |||
WRN | ENST00000651642.1 | c.20-3del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||||
WRN | ENST00000650667.1 | c.*339-3del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151958Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251284Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135852
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1457384Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 725350
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151958Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74202
ClinVar
Submissions by phenotype
Werner syndrome Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 11, 2022 | This sequence change falls in intron 7 of the WRN gene. It does not directly change the encoded amino acid sequence of the WRN protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs778493200, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with WRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 362796). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 12, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at