rs150233736
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_006063.3(KLHL41):c.832G>A(p.Val278Met) variant causes a missense change. The variant allele was found at a frequency of 0.000301 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V278A) has been classified as Uncertain significance.
Frequency
Consequence
NM_006063.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLHL41 | NM_006063.3 | c.832G>A | p.Val278Met | missense_variant | 1/6 | ENST00000284669.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHL41 | ENST00000284669.2 | c.832G>A | p.Val278Met | missense_variant | 1/6 | 1 | NM_006063.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000235 AC: 59AN: 251468Hom.: 0 AF XY: 0.000221 AC XY: 30AN XY: 135916
GnomAD4 exome AF: 0.000315 AC: 461AN: 1461888Hom.: 0 Cov.: 33 AF XY: 0.000298 AC XY: 217AN XY: 727246
GnomAD4 genome AF: 0.000164 AC: 25AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74340
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 16, 2023 | The c.832G>A (p.V278M) alteration is located in exon 1 (coding exon 1) of the KLHL41 gene. This alteration results from a G to A substitution at nucleotide position 832, causing the valine (V) at amino acid position 278 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
KLHL41-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 27, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Nemaline myopathy 9 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at