19-18668116-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_018316.3(KLHL26):c.719G>A(p.Arg240Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,601,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
KLHL26
NM_018316.3 missense
NM_018316.3 missense
Scores
10
7
2
Clinical Significance
Conservation
PhyloP100: 7.84
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.951
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLHL26 | NM_018316.3 | c.719G>A | p.Arg240Gln | missense_variant | 3/3 | ENST00000300976.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHL26 | ENST00000300976.9 | c.719G>A | p.Arg240Gln | missense_variant | 3/3 | 1 | NM_018316.3 | P1 | |
KLHL26 | ENST00000599006.5 | c.405+314G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152192Hom.: 0 Cov.: 33
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?
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GnomAD3 exomes AF: 0.0000223 AC: 5AN: 224484Hom.: 0 AF XY: 0.0000160 AC XY: 2AN XY: 124808
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GnomAD4 exome AF: 0.0000138 AC: 20AN: 1449034Hom.: 0 Cov.: 34 AF XY: 0.0000125 AC XY: 9AN XY: 720868
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74350
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 25, 2023 | The c.719G>A (p.R240Q) alteration is located in exon 3 (coding exon 3) of the KLHL26 gene. This alteration results from a G to A substitution at nucleotide position 719, causing the arginine (R) at amino acid position 240 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0273);
MVP
MPC
ClinPred
D
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