4-44448160-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_198353.3(KCTD8):c.364G>A(p.Glu122Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 1,612,414 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
KCTD8
NM_198353.3 missense
NM_198353.3 missense
Scores
3
10
6
Clinical Significance
Conservation
PhyloP100: 7.70
Genes affected
KCTD8 (HGNC:22394): (potassium channel tetramerization domain containing 8) Predicted to be involved in regulation of G protein-coupled receptor signaling pathway. Predicted to be located in cell projection; postsynaptic membrane; and presynaptic membrane. Predicted to be integral component of membrane. Predicted to be part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCTD8 | NM_198353.3 | c.364G>A | p.Glu122Lys | missense_variant | 1/2 | ENST00000360029.4 | |
KCTD8 | XM_011513690.4 | c.364G>A | p.Glu122Lys | missense_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCTD8 | ENST00000360029.4 | c.364G>A | p.Glu122Lys | missense_variant | 1/2 | 1 | NM_198353.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000790 AC: 12AN: 151978Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000609 AC: 15AN: 246208Hom.: 0 AF XY: 0.0000669 AC XY: 9AN XY: 134464
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GnomAD4 exome AF: 0.000114 AC: 167AN: 1460436Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 78AN XY: 726536
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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 | Jan 22, 2024 | The c.364G>A (p.E122K) alteration is located in exon 1 (coding exon 1) of the KCTD8 gene. This alteration results from a G to A substitution at nucleotide position 364, causing the glutamic acid (E) at amino acid position 122 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
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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