chr19-18637113-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_018316.3(KLHL26):c.59G>A(p.Gly20Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000022 in 1,364,226 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000017 ( 0 hom. )
Consequence
KLHL26
NM_018316.3 missense
NM_018316.3 missense
Scores
3
2
14
Clinical Significance
Conservation
PhyloP100: 0.855
Genes affected
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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=0.18731025).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLHL26 | NM_018316.3 | c.59G>A | p.Gly20Asp | missense_variant | 1/3 | ENST00000300976.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHL26 | ENST00000300976.9 | c.59G>A | p.Gly20Asp | missense_variant | 1/3 | 1 | NM_018316.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152228Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000165 AC: 2AN: 1211998Hom.: 0 Cov.: 31 AF XY: 0.00000170 AC XY: 1AN XY: 588552
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74376
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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 | Aug 15, 2023 | The c.59G>A (p.G20D) alteration is located in exon 1 (coding exon 1) of the KLHL26 gene. This alteration results from a G to A substitution at nucleotide position 59, causing the glycine (G) at amino acid position 20 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.
MutationTaster
Benign
N
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;.;.
REVEL
Benign
Sift
Benign
D;.;.
Sift4G
Pathogenic
D;D;D
Polyphen
B;.;.
Vest4
MutPred
Loss of catalytic residue at A19 (P = 0.1169);Loss of catalytic residue at A19 (P = 0.1169);Loss of catalytic residue at A19 (P = 0.1169);
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