2-169509792-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006063.3(KLHL41):c.14G>A(p.Arg5Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,458,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R5R) has been classified as Likely benign.
Frequency
Consequence
NM_006063.3 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 |
---|---|---|---|---|---|---|---|
KLHL41 | NM_006063.3 | c.14G>A | p.Arg5Gln | missense_variant | 1/6 | ENST00000284669.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHL41 | ENST00000284669.2 | c.14G>A | p.Arg5Gln | missense_variant | 1/6 | 1 | NM_006063.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000805 AC: 2AN: 248416Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134486
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1458456Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 725560
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Nemaline myopathy 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2021 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with KLHL41-related conditions. This variant is present in population databases (rs747822404, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 5 of the KLHL41 protein (p.Arg5Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at