19-18668254-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_018316.3(KLHL26):c.857A>G(p.Asn286Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000571 in 1,612,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000032 ( 0 hom. )
Consequence
KLHL26
NM_018316.3 missense
NM_018316.3 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 5.04
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.030468553).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLHL26 | NM_018316.3 | c.857A>G | p.Asn286Ser | missense_variant | 3/3 | ENST00000300976.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHL26 | ENST00000300976.9 | c.857A>G | p.Asn286Ser | missense_variant | 3/3 | 1 | NM_018316.3 | P1 | |
KLHL26 | ENST00000599006.5 | c.405+452A>G | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000302 AC: 46AN: 152218Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000979 AC: 24AN: 245220Hom.: 0 AF XY: 0.0000374 AC XY: 5AN XY: 133820
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GnomAD4 exome AF: 0.0000315 AC: 46AN: 1459832Hom.: 0 Cov.: 34 AF XY: 0.0000262 AC XY: 19AN XY: 726194
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GnomAD4 genome ? AF: 0.000302 AC: 46AN: 152336Hom.: 0 Cov.: 33 AF XY: 0.000295 AC XY: 22AN XY: 74490
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Asia WGS
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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 06, 2021 | The c.857A>G (p.N286S) alteration is located in exon 3 (coding exon 3) of the KLHL26 gene. This alteration results from a A to G substitution at nucleotide position 857, causing the asparagine (N) at amino acid position 286 to be replaced by a serine (S). 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
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
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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