rs137854492
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP2PP3
The NM_001363.5(DKC1):c.1069A>G(p.Thr357Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. T357S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001363.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DKC1 | NM_001363.5 | c.1069A>G | p.Thr357Ala | missense_variant | 11/15 | ENST00000369550.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DKC1 | ENST00000369550.10 | c.1069A>G | p.Thr357Ala | missense_variant | 11/15 | 1 | NM_001363.5 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD4 exome Cov.: 29
GnomAD4 genome ? Cov.: 22
ClinVar
Submissions by phenotype
Dyskeratosis congenita, X-linked Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2005 | - - |
Dyskeratosis congenita Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 04, 2019 | The p.T357A variant (also known as c.1069A>G), located in coding exon 11 of the DKC1 gene, results from an A to G substitution at nucleotide position 1069. The threonine at codon 357 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on internal structural analysis, this variant is anticipated to result in a change in protein-protein interaction. However, it does not disrupt the surface structure itself (Li S et al. EMBO J., 2011 Nov;30:5010-20). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at