NM_198317.3:c.136C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198317.3(KLHL17):​c.136C>A​(p.Gln46Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

KLHL17
NM_198317.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70
Variant links:
Genes affected
KLHL17 (HGNC:24023): (kelch like family member 17) The protein encoded by this gene is expressed in neurons of most regions of the brain. It contains an N-terminal BTB domain, which mediates dimerization of the protein, and a C-terminal Kelch domain, which mediates binding to F-actin. This protein may play a key role in the regulation of actin-based neuronal function. [provided by RefSeq, Aug 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10923612).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KLHL17NM_198317.3 linkc.136C>A p.Gln46Lys missense_variant Exon 2 of 12 ENST00000338591.8 NP_938073.1 Q6TDP4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KLHL17ENST00000338591.8 linkc.136C>A p.Gln46Lys missense_variant Exon 2 of 12 1 NM_198317.3 ENSP00000343930.3 Q6TDP4
KLHL17ENST00000463212.1 linkn.-128C>A upstream_gene_variant 1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.136C>A (p.Q46K) alteration is located in exon 2 (coding exon 2) of the KLHL17 gene. This alteration results from a C to A substitution at nucleotide position 136, causing the glutamine (Q) at amino acid position 46 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
21
DANN
Benign
0.70
DEOGEN2
Benign
0.038
T
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.54
FATHMM_MKL
Benign
0.58
D
LIST_S2
Benign
0.60
T
M_CAP
Benign
0.068
D
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
-0.33
N
REVEL
Benign
0.20
Sift
Benign
0.68
T
Sift4G
Benign
0.94
T
Polyphen
0.0010
B
Vest4
0.22
MutPred
0.26
Gain of ubiquitination at Q46 (P = 0.0085);
MVP
0.66
ClinPred
0.073
T
GERP RS
3.6
Varity_R
0.21
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-896701; API