17-41845328-T-C
Variant names:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_152467.5(KLHL10):c.887T>C(p.Ile296Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00797 in 1,614,174 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0056 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0082 ( 75 hom. )
Consequence
KLHL10
NM_152467.5 missense
NM_152467.5 missense
Scores
11
7
Clinical Significance
Conservation
PhyloP100: 3.62
Genes affected
KLHL10 (HGNC:18829): (kelch like family member 10) The protein encoded by this gene belongs to the kelch repeat-containing family, and contains an N-terminal BTB/POZ domain a BACK domain and six C-terminal kelch repeats. Kelch domains are thought to form a four stranded beta-sheet blade structure that can fold into a beta-propeller domain when multiple kelch repeats are found together. Mutations in this gene have been associated with oligozoospermia in some infertile males. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.01672268).
BP6
Variant 17-41845328-T-C is Benign according to our data. Variant chr17-41845328-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 684737.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1, Likely_benign=1}.
BS2
High AC in GnomAd4 at 850 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KLHL10 | NM_152467.5 | c.887T>C | p.Ile296Thr | missense_variant | Exon 3 of 5 | ENST00000293303.5 | NP_689680.2 | |
KLHL10 | NM_001329595.1 | c.887T>C | p.Ile296Thr | missense_variant | Exon 5 of 7 | NP_001316524.1 | ||
KLHL10 | NM_001329596.2 | c.623T>C | p.Ile208Thr | missense_variant | Exon 3 of 5 | NP_001316525.1 | ||
KLHL10 | XM_047435897.1 | c.887T>C | p.Ile296Thr | missense_variant | Exon 4 of 6 | XP_047291853.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00559 AC: 850AN: 152188Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.00546 AC: 1361AN: 249422Hom.: 5 AF XY: 0.00550 AC XY: 744AN XY: 135322
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GnomAD4 exome AF: 0.00822 AC: 12014AN: 1461868Hom.: 75 Cov.: 32 AF XY: 0.00789 AC XY: 5739AN XY: 727232
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GnomAD4 genome AF: 0.00558 AC: 850AN: 152306Hom.: 4 Cov.: 32 AF XY: 0.00485 AC XY: 361AN XY: 74482
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2025 | KLHL10: PP2, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 31, 2019 | - - |
Non-obstructive azoospermia Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Institute of Reproductive Genetics, University of Münster | Jun 07, 2020 | - - |
KLHL10-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 18, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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