GeneBe

rs1401268433

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001142730.3(KCTD1):​c.2555G>T​(p.Arg852Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R852H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

KCTD1
NM_001142730.3 missense

Scores

1
6
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.81

Publications

1 publications found
Variant links:
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]
KCTD1 Gene-Disease associations (from GenCC):
  • scalp-ear-nipple syndrome
    Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.41524628).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142730.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
KCTD1
NM_001142730.3
MANE Select
c.2555G>Tp.Arg852Leu
missense
Exon 5 of 5NP_001136202.1A0A2U3U043
KCTD1
NM_001258222.3
c.755G>Tp.Arg252Leu
missense
Exon 5 of 5NP_001245151.1
KCTD1
NM_001136205.2
c.731G>Tp.Arg244Leu
missense
Exon 5 of 5NP_001129677.1Q719H9

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
KCTD1
ENST00000580059.7
TSL:3 MANE Select
c.2555G>Tp.Arg852Leu
missense
Exon 5 of 5ENSP00000463041.2A0A2U3U043
KCTD1
ENST00000408011.7
TSL:1
c.731G>Tp.Arg244Leu
missense
Exon 5 of 5ENSP00000384367.3Q719H9
KCTD1
ENST00000579973.5
TSL:1
c.731G>Tp.Arg244Leu
missense
Exon 6 of 6ENSP00000464170.1Q719H9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.12
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.021
T
Eigen
Benign
0.021
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.42
T
MetaSVM
Benign
-0.57
T
MutationAssessor
Benign
1.1
L
PhyloP100
3.8
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-1.2
N
REVEL
Uncertain
0.33
Sift
Benign
0.19
T
Sift4G
Benign
0.22
T
Polyphen
0.15
B
Vest4
0.34
MutPred
0.34
Loss of MoRF binding (P = 0.01)
MVP
0.70
MPC
0.79
ClinPred
0.73
D
GERP RS
6.0
Varity_R
0.42
gMVP
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1401268433; hg19: chr18-24035750; API