chr8-31157398-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000553.6(WRN):c.3850C>T(p.Leu1284Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L1284H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000553.6 missense
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.3850C>T | p.Leu1284Phe | missense_variant | 33/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.3850C>T | p.Leu1284Phe | missense_variant | 33/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000521620.5 | n.2483C>T | non_coding_transcript_exon_variant | 21/23 | 1 | ||||
WRN | ENST00000650667.1 | c.*3464C>T | 3_prime_UTR_variant, NMD_transcript_variant | 32/34 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461820Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727224
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Werner syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 24, 2023 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 572355). This variant has not been reported in the literature in individuals affected with WRN-related conditions. This variant is present in population databases (rs368876038, gnomAD 0.007%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1284 of the WRN protein (p.Leu1284Phe). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at