3-183650217-G-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_017644.3(KLHL24):c.-61-79G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 636,122 control chromosomes in the GnomAD database, including 27,578 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.32 ( 8193 hom., cov: 32)
Exomes 𝑓: 0.27 ( 19385 hom. )
Consequence
KLHL24
NM_017644.3 intron
NM_017644.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.504
Genes affected
KLHL24 (HGNC:25947): (kelch like family member 24) The protein encoded by this gene is a ubiquitin ligase substrate receptor and is regulated by autoubiquitination. Variations in the translation initiation codon of this gene have been found, which result in an N-terminally truncated but more stable protein due to loss of the autoubiquitination function. The more stable mutant protein causes an increased ubiquitin and degradation of keratin 14, which leads to skin fragility and the potentially life-threatening disease epidermolysis bullosa. The encoded protein is also involved in the regulation of kainate receptors. [provided by RefSeq, Mar 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 3-183650217-G-A is Benign according to our data. Variant chr3-183650217-G-A is described in ClinVar as [Benign]. Clinvar id is 1288159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KLHL24 | NM_017644.3 | c.-61-79G>A | intron_variant | ENST00000242810.11 | NP_060114.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KLHL24 | ENST00000242810.11 | c.-61-79G>A | intron_variant | 1 | NM_017644.3 | ENSP00000242810.6 |
Frequencies
GnomAD3 genomes AF: 0.318 AC: 48262AN: 151884Hom.: 8183 Cov.: 32
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GnomAD4 exome AF: 0.274 AC: 132614AN: 484120Hom.: 19385 AF XY: 0.269 AC XY: 68093AN XY: 253044
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GnomAD4 genome AF: 0.318 AC: 48313AN: 152002Hom.: 8193 Cov.: 32 AF XY: 0.313 AC XY: 23243AN XY: 74296
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at