1-6593380-G-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_014851.4(KLHL21):c.1779C>T(p.Pro593Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000447 in 1,597,940 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: 𝑓 0.0024 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00024 ( 1 hom. )
Consequence
KLHL21
NM_014851.4 synonymous
NM_014851.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.84
Genes affected
KLHL21 (HGNC:29041): (kelch like family member 21) Enables cullin family protein binding activity. Contributes to ubiquitin-protein transferase activity. Involved in chromosome passenger complex localization to spindle midzone; protein ubiquitination; and regulation of cytokinesis. Located in polar microtubule. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 1-6593380-G-A is Benign according to our data. Variant chr1-6593380-G-A is described in ClinVar as [Benign]. Clinvar id is 3035585.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-1.84 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KLHL21 | ENST00000377658.8 | c.1779C>T | p.Pro593Pro | synonymous_variant | 4/4 | 1 | NM_014851.4 | ENSP00000366886.4 | ||
KLHL21 | ENST00000377663 | c.*1985C>T | 3_prime_UTR_variant | 3/3 | 1 | ENSP00000366891.3 | ||||
KLHL21 | ENST00000467612.5 | c.678C>T | p.Pro226Pro | synonymous_variant | 4/4 | 3 | ENSP00000466089.1 | |||
KLHL21 | ENST00000496707.5 | c.*1C>T | downstream_gene_variant | 1 | ENSP00000468710.1 |
Frequencies
GnomAD3 genomes AF: 0.00238 AC: 363AN: 152208Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.000648 AC: 155AN: 239278Hom.: 1 AF XY: 0.000428 AC XY: 56AN XY: 130708
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GnomAD4 exome AF: 0.000243 AC: 351AN: 1445614Hom.: 1 Cov.: 31 AF XY: 0.000237 AC XY: 170AN XY: 718072
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GnomAD4 genome AF: 0.00239 AC: 364AN: 152326Hom.: 3 Cov.: 33 AF XY: 0.00230 AC XY: 171AN XY: 74482
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
KLHL21-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 06, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
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