chr11-65526146-AC-A
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_020680.4(SCYL1):c.399del(p.Asn133LysfsTer136) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,612,980 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
SCYL1
NM_020680.4 frameshift
NM_020680.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.0920
Genes affected
SCYL1 (HGNC:14372): (SCY1 like pseudokinase 1) This gene encodes a transcriptional regulator belonging to the SCY1-like family of kinase-like proteins. The protein has a divergent N-terminal kinase domain that is thought to be catalytically inactive, and can bind specific DNA sequences through its C-terminal domain. It activates transcription of the telomerase reverse transcriptase and DNA polymerase beta genes. The protein has been localized to the nucleus, and also to the cytoplasm and centrosomes during mitosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 11-65526146-AC-A is Pathogenic according to our data. Variant chr11-65526146-AC-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 422875.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=1, Pathogenic=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCYL1 | NM_020680.4 | c.399del | p.Asn133LysfsTer136 | frameshift_variant | 4/18 | ENST00000270176.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCYL1 | ENST00000270176.10 | c.399del | p.Asn133LysfsTer136 | frameshift_variant | 4/18 | 1 | NM_020680.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152106Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000283 AC: 7AN: 247480Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134834
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GnomAD4 exome AF: 0.0000356 AC: 52AN: 1460874Hom.: 0 Cov.: 33 AF XY: 0.0000261 AC XY: 19AN XY: 726754
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152106Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74302
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 27, 2018 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 01, 2019 | Frameshift variant predicted to result in nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at