rs201856772
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_152393.4(KLHL40):c.1762G>A(p.Glu588Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00047 in 1,598,414 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_152393.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00166 AC: 245AN: 147540Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000663 AC: 166AN: 250232Hom.: 0 AF XY: 0.000576 AC XY: 78AN XY: 135320
GnomAD4 exome AF: 0.000349 AC: 507AN: 1450760Hom.: 2 Cov.: 29 AF XY: 0.000332 AC XY: 240AN XY: 722738
GnomAD4 genome AF: 0.00165 AC: 244AN: 147654Hom.: 0 Cov.: 31 AF XY: 0.00172 AC XY: 124AN XY: 72266
ClinVar
Submissions by phenotype
Nemaline myopathy 8 Uncertain:1Benign:1
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This variant (GRCh38; NM_152393.4:c.1762G>A:p.Glu588Lys) results in a missense mutation with the conversion of Glutamate (Acidic amino acid) to Lysine (Basic amino acid) in the KLHL40 protein. This variant has a strong Conservation score. Multiple lines of computational evidence support a deleterious effect on the gene or gene product for this variant. Reputable source recently reports variant as benign. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. This variant is associated with the following publications: PubMed: 20301465, 23746549, 27528495, 26754003, 27762439. Based on conflicting evidence or insufficient data to determine whether the variant is benign or pathogenic, the clinical significance of this alteration remains unclear. In summary, this variant meets our criteria for classification as of Unknown Clinical Significance based on the evidence outlined. -
not provided Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at