rs34020089
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_152393.4(KLHL40):c.1761C>G(p.Asn587Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,602,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_152393.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLHL40 | NM_152393.4 | c.1761C>G | p.Asn587Lys | missense_variant | 6/6 | ENST00000287777.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHL40 | ENST00000287777.5 | c.1761C>G | p.Asn587Lys | missense_variant | 6/6 | 1 | NM_152393.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152110Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250158Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135288
GnomAD4 exome AF: 0.00000827 AC: 12AN: 1450808Hom.: 0 Cov.: 28 AF XY: 0.00000830 AC XY: 6AN XY: 722520
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74304
ClinVar
Submissions by phenotype
Nemaline myopathy 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 04, 2022 | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 574846). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 587 of the KLHL40 protein (p.Asn587Lys). This variant is present in population databases (rs34020089, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with KLHL40-related conditions. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 06, 2020 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at