13-76885542-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138444.4(KCTD12):​c.607G>A​(p.Gly203Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 1,414,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

KCTD12
NM_138444.4 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.83
Variant links:
Genes affected
KCTD12 (HGNC:14678): (potassium channel tetramerization domain containing 12) Enables identical protein binding activity. Predicted to be involved in protein homooligomerization. Predicted to act upstream of or within regulation of G protein-coupled receptor signaling pathway. Predicted to be located in cell projection. Predicted to be part of receptor complex. Predicted to be active in postsynaptic membrane and presynaptic membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.0901086).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KCTD12NM_138444.4 linkuse as main transcriptc.607G>A p.Gly203Ser missense_variant 1/1 ENST00000377474.4 NP_612453.1 Q96CX2A0A140VJM4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KCTD12ENST00000377474.4 linkuse as main transcriptc.607G>A p.Gly203Ser missense_variant 1/16 NM_138444.4 ENSP00000366694.2 Q96CX2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000283
AC:
4
AN:
1414772
Hom.:
0
Cov.:
31
AF XY:
0.00000571
AC XY:
4
AN XY:
701114
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000366
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000325
Hom.:
0

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 submitterclinical testingAmbry GeneticsSep 30, 2024The c.607G>A (p.G203S) alteration is located in exon 1 (coding exon 1) of the KCTD12 gene. This alteration results from a G to A substitution at nucleotide position 607, causing the glycine (G) at amino acid position 203 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.62
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.031
T
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.21
FATHMM_MKL
Benign
0.51
D
LIST_S2
Benign
0.33
T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.090
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-0.79
N
REVEL
Benign
0.12
Sift
Benign
0.34
T
Sift4G
Benign
0.44
T
Polyphen
0.018
B
Vest4
0.034
MutPred
0.32
Gain of catalytic residue at R206 (P = 9e-04);
MVP
0.55
MPC
0.99
ClinPred
0.70
D
GERP RS
4.5
Varity_R
0.19
gMVP
0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs990400634; hg19: chr13-77459677; API