chr18-26459645-C-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_001142730.3(KCTD1):c.2414G>C(p.Gly805Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000175 in 1,601,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
KCTD1
NM_001142730.3 missense
NM_001142730.3 missense
Scores
4
7
4
Clinical Significance
Conservation
PhyloP100: 5.79
Genes affected
KCTD1 (HGNC:18249): (potassium channel tetramerization domain containing 1) This gene encodes a protein containing a BTB (Broad-complex, tramtrack and bric a brac), also known as a POZ (POxvirus and zinc finger) protein-protein interaction domain. The encoded protein negatively regulates the AP-2 family of transcription factors and the Wnt signaling pathway. A mechanism for the modulation of Wnt signaling has been proposed in which the encoded protein enhances ubiquitination and degradation of the beta-catenin protein. Mutations in this gene have been identified in Scalp-ear-nipple (SEN) syndrome. [provided by RefSeq, May 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.802
BS2
?
High AC in GnomAd at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCTD1 | NM_001142730.3 | c.2414G>C | p.Gly805Ala | missense_variant | 4/5 | ENST00000580059.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCTD1 | ENST00000580059.7 | c.2414G>C | p.Gly805Ala | missense_variant | 4/5 | 3 | NM_001142730.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152180Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000820 AC: 2AN: 243826Hom.: 0 AF XY: 0.00000760 AC XY: 1AN XY: 131496
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GnomAD4 exome AF: 0.0000159 AC: 23AN: 1449774Hom.: 0 Cov.: 32 AF XY: 0.0000195 AC XY: 14AN XY: 719126
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152180Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74350
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 03, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 197 of the KCTD1 protein (p.Gly197Ala). This variant is present in population databases (rs377664171, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with KCTD1-related conditions. 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. 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;T;T;.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M;M;M;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
Sift4G
Benign
T;T;T;T;.;.;.
Polyphen
P;P;P;P;.;.;.
Vest4
MVP
MPC
1.4
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