chr10-69300862-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PVS1_Moderate
The NM_033500.2(HK1):c.27+1G>C variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Consequence
NM_033500.2 splice_donor, 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HK1 | NM_001358263.1 | c.75+5182G>C | intron_variant | Intron 4 of 20 | ENST00000643399.2 | NP_001345192.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152070Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000827 AC: 2AN: 241740Hom.: 0 AF XY: 0.00000765 AC XY: 1AN XY: 130694
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000508 AC: 7AN: 1379004Hom.: 0 Cov.: 21 AF XY: 0.00000579 AC XY: 4AN XY: 690268
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152070Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74272
ClinVar
Submissions by phenotype
HK1-related disorder Uncertain:1
The HK1 c.27+1G>C variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has been reported in an individual with autosomal dominant retinitis pigmentosa (Table S4, Kim et al. 2021. PubMed ID: 33946315). This variant is reported in 0.010% of alleles in individuals of East Asian descent in gnomAD. Loss of function variants in HK1 are not a well-established mechanism of disease. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at