chr4-44448403-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_198353.3(KCTD8):c.121C>T(p.Pro41Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000323 in 1,576,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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: 0.000035 ( 0 hom. )
Consequence
KCTD8
NM_198353.3 missense
NM_198353.3 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 6.57
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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.18897855).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCTD8 | NM_198353.3 | c.121C>T | p.Pro41Ser | missense_variant | 1/2 | ENST00000360029.4 | |
KCTD8 | XM_011513690.4 | c.121C>T | p.Pro41Ser | missense_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCTD8 | ENST00000360029.4 | c.121C>T | p.Pro41Ser | missense_variant | 1/2 | 1 | NM_198353.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000659 AC: 1AN: 151860Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000148 AC: 3AN: 202476Hom.: 0 AF XY: 0.0000179 AC XY: 2AN XY: 111986
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GnomAD4 exome AF: 0.0000351 AC: 50AN: 1425002Hom.: 0 Cov.: 32 AF XY: 0.0000353 AC XY: 25AN XY: 707640
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151978Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74266
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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 | Mar 01, 2023 | The c.121C>T (p.P41S) alteration is located in exon 1 (coding exon 1) of the KCTD8 gene. This alteration results from a C to T substitution at nucleotide position 121, causing the proline (P) at amino acid position 41 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
Benign
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MVP
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