chr4-44175041-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_198353.3(KCTD8):c.1171C>T(p.Arg391Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,613,966 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
KCTD8
NM_198353.3 missense
NM_198353.3 missense
Scores
3
9
7
Clinical Significance
Conservation
PhyloP100: 2.12
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.1171C>T | p.Arg391Cys | missense_variant | 2/2 | ENST00000360029.4 | |
KCTD8 | XM_011513690.4 | c.1255C>T | p.Arg419Cys | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCTD8 | ENST00000360029.4 | c.1171C>T | p.Arg391Cys | missense_variant | 2/2 | 1 | NM_198353.3 | P1 | |
KCTD8 | ENST00000515268.1 | c.379C>T | p.Arg127Cys | missense_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152056Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251348Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135854
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GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461792Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 727198
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74398
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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 16, 2021 | The c.1171C>T (p.R391C) alteration is located in exon 2 (coding exon 2) of the KCTD8 gene. This alteration results from a C to T substitution at nucleotide position 1171, causing the arginine (R) at amino acid position 391 to be replaced by a cysteine (C). 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
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of ubiquitination at K394 (P = 0.0399);
MVP
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