GeneBe

chr13-76885615-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_138444.4(KCTD12):​c.534G>A​(p.Thr178Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000739 in 1,352,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 7.4e-7 ( 0 hom. )

Consequence

KCTD12
NM_138444.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.642

Publications

0 publications found
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]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP7
Synonymous conserved (PhyloP=-0.642 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCTD12NM_138444.4 linkc.534G>A p.Thr178Thr synonymous_variant Exon 1 of 1 ENST00000377474.4 NP_612453.1 Q96CX2A0A140VJM4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCTD12ENST00000377474.4 linkc.534G>A p.Thr178Thr synonymous_variant Exon 1 of 1 6 NM_138444.4 ENSP00000366694.2 Q96CX2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.39e-7
AC:
1
AN:
1352574
Hom.:
0
Cov.:
31
AF XY:
0.00000150
AC XY:
1
AN XY:
666826
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
29086
American (AMR)
AF:
0.00
AC:
0
AN:
28892
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22012
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35150
South Asian (SAS)
AF:
0.00
AC:
0
AN:
73002
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
34106
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4188
European-Non Finnish (NFE)
AF:
9.35e-7
AC:
1
AN:
1069876
Other (OTH)
AF:
0.00
AC:
0
AN:
56262
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
CADD
Benign
11
DANN
Benign
0.97
PhyloP100
-0.64

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: rs34544607; hg19: chr13-77459750; API