rs375754573
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_152393.4(KLHL40):c.486G>A(p.Leu162=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000893 in 1,600,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000095 ( 0 hom. )
Consequence
KLHL40
NM_152393.4 synonymous
NM_152393.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0940
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 Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 3-42686104-G-A is Benign according to our data. Variant chr3-42686104-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 570969.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.094 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLHL40 | NM_152393.4 | c.486G>A | p.Leu162= | synonymous_variant | 1/6 | ENST00000287777.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHL40 | ENST00000287777.5 | c.486G>A | p.Leu162= | synonymous_variant | 1/6 | 1 | NM_152393.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152202Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000208 AC: 5AN: 240792Hom.: 0 AF XY: 0.0000229 AC XY: 3AN XY: 131192
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GnomAD4 exome AF: 0.0000953 AC: 138AN: 1448554Hom.: 0 Cov.: 30 AF XY: 0.0000915 AC XY: 66AN XY: 721070
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152320Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74478
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Nemaline myopathy 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 29, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at