rs147863385
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_152393.4(KLHL40):c.1104C>T(p.Phe368=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00841 in 1,613,298 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0063 ( 5 hom., cov: 33)
Exomes 𝑓: 0.0086 ( 69 hom. )
Consequence
KLHL40
NM_152393.4 synonymous
NM_152393.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.407
Genes affected
KLHL40 (HGNC:30372): (kelch like family member 40) This gene encodes a protein containing a BACK domain, a BTB/POZ domain, and 5 Kelch repeats, however, its exact function is not known. The gene and the multi-domain protein structure are conserved across different taxa, including primates, rodents, chicken and zebrafish. [provided by RefSeq, Dec 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 3-42686722-C-T is Benign according to our data. Variant chr3-42686722-C-T is described in ClinVar as [Benign]. Clinvar id is 262640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.407 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00632 (962/152328) while in subpopulation NFE AF= 0.0101 (688/68034). AF 95% confidence interval is 0.00949. There are 5 homozygotes in gnomad4. There are 449 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLHL40 | NM_152393.4 | c.1104C>T | p.Phe368= | synonymous_variant | 1/6 | ENST00000287777.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHL40 | ENST00000287777.5 | c.1104C>T | p.Phe368= | synonymous_variant | 1/6 | 1 | NM_152393.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00632 AC: 962AN: 152210Hom.: 5 Cov.: 33
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GnomAD3 exomes AF: 0.00627 AC: 1569AN: 250244Hom.: 10 AF XY: 0.00632 AC XY: 856AN XY: 135508
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GnomAD4 exome AF: 0.00863 AC: 12603AN: 1460970Hom.: 69 Cov.: 34 AF XY: 0.00843 AC XY: 6124AN XY: 726792
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GnomAD4 genome ? AF: 0.00632 AC: 962AN: 152328Hom.: 5 Cov.: 33 AF XY: 0.00603 AC XY: 449AN XY: 74474
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 25, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 26, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 07, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | KLHL40: BP4, BS1, BS2 - |
Nemaline myopathy 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at