chr3-49172969-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_173546.3(KLHDC8B):c.200C>T(p.Thr67Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000109 in 1,461,640 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
KLHDC8B
NM_173546.3 missense
NM_173546.3 missense
Scores
4
10
5
Clinical Significance
Conservation
PhyloP100: 6.04
Genes affected
KLHDC8B (HGNC:28557): (kelch domain containing 8B) This gene encodes a protein which forms a distinct beta-propeller protein structure of kelch domains allowing for protein-protein interactions. Mutations in this gene have been associated with Hodgkin lymphoma. [provided by RefSeq, Sep 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLHDC8B | NM_173546.3 | c.200C>T | p.Thr67Ile | missense_variant | 2/6 | ENST00000332780.4 | |
KLHDC8B | XM_006713015.4 | c.200C>T | p.Thr67Ile | missense_variant | 2/6 | ||
KLHDC8B | XM_006713016.4 | c.200C>T | p.Thr67Ile | missense_variant | 2/6 | ||
KLHDC8B | XM_005264938.4 | c.200C>T | p.Thr67Ile | missense_variant | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHDC8B | ENST00000332780.4 | c.200C>T | p.Thr67Ile | missense_variant | 2/6 | 1 | NM_173546.3 | P1 | |
KLHDC8B | ENST00000476495.2 | n.257C>T | non_coding_transcript_exon_variant | 1/3 | 2 | ||||
KLHDC8B | ENST00000459846.6 | n.230+168C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250658Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135686
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461640Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727170
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 22, 2024 | The c.200C>T (p.T67I) alteration is located in exon 2 (coding exon 1) of the KLHDC8B gene. This alteration results from a C to T substitution at nucleotide position 200, causing the threonine (T) at amino acid position 67 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 03, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with KLHDC8B-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 67 of the KLHDC8B protein (p.Thr67Ile). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of glycosylation at P64 (P = 0.0339);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at