chr4-44448114-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_198353.3(KCTD8):c.410T>A(p.Phe137Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000297 in 1,612,454 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00027 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00030 ( 0 hom. )
Consequence
KCTD8
NM_198353.3 missense
NM_198353.3 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 9.03
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 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3737898).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCTD8 | NM_198353.3 | c.410T>A | p.Phe137Tyr | missense_variant | 1/2 | ENST00000360029.4 | |
KCTD8 | XM_011513690.4 | c.410T>A | p.Phe137Tyr | missense_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCTD8 | ENST00000360029.4 | c.410T>A | p.Phe137Tyr | missense_variant | 1/2 | 1 | NM_198353.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000270 AC: 41AN: 151734Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000200 AC: 49AN: 245166Hom.: 0 AF XY: 0.000194 AC XY: 26AN XY: 133994
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GnomAD4 exome AF: 0.000300 AC: 438AN: 1460602Hom.: 0 Cov.: 32 AF XY: 0.000274 AC XY: 199AN XY: 726626
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GnomAD4 genome ? AF: 0.000270 AC: 41AN: 151852Hom.: 1 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74178
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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 13, 2021 | The c.410T>A (p.F137Y) alteration is located in exon 1 (coding exon 1) of the KCTD8 gene. This alteration results from a T to A substitution at nucleotide position 410, causing the phenylalanine (F) at amino acid position 137 to be replaced by a tyrosine (Y). 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
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
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