NM_021615.5:c.892C>T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_021615.5(CHST6):c.892C>T(p.Gln298*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_021615.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250212Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135686
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460774Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6AN XY: 726730
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Macular corneal dystrophy Pathogenic:1
The CHST6 c.892C>T (p.Gln298Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. The p.Gln298Ter variant has been reported in two studies in which it is found in a total of 11 patients with macular corneal dystrophy, including in two from the same family in a homozygous state, in nine in a compound heterozygous state (at least three of whom are related), and in a heterozygous state in three unaffected family members (Dang et al. 2009; Liu et al. 2010). The p.Gln298Ter variant was absent from 150 controls and is not found in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium. Based on the evidence and the potential impact of stop-gained variants, the p.Gln298Ter variant is classified as pathogenic for macular corneal dystrophy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at