Variant 17-7353504-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001363642.1(KCTD11):c.679C>T(p.Arg227Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,593,704 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: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

KCTD11
NM_001363642.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.275

Variant links:

Genes affected

KCTD11 (HGNC:21302): (potassium channel tetramerization domain containing 11) Enables identical protein binding activity. Predicted to be involved in positive regulation of neuron differentiation. Predicted to act upstream of or within negative regulation of neuroblast proliferation and negative regulation of smoothened signaling pathway. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

KCTD11 links:

ENSG00000263171 (HGNC:):

ENSG00000263171 links:

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=0.15813503).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD11	NM_001363642.1 linkuse as main transcript	c.679C>T	p.Arg227Trp	missense_variant	1/1	ENST00000333751.8	NP_001350571.1
KCTD11	NM_001002914.3 linkuse as main transcript	c.562C>T	p.Arg188Trp	missense_variant	1/1		NP_001002914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KCTD11	ENST00000333751.8 linkuse as main transcript	c.679C>T	p.Arg227Trp	missense_variant	1/1	6	NM_001363642.1	ENSP00000328352.5	Q693B1-2A0A2U3TZI5
KCTD11	ENST00000576980.2 linkuse as main transcript	c.562C>T	p.Arg188Trp	missense_variant	1/1	6		ENSP00000495203.1	Q693B1-1
ENSG00000263171	ENST00000572417.1 linkuse as main transcript	n.276-672G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000424

AC:

AN:

235596

Hom.:

AF XY:

0.0000312

AC XY:

AN XY:

128410

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000179

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000104

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1441510

Hom.:

Cov.:

AF XY:

0.00000980

AC XY:

AN XY:

714332

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000160

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000826

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.09e-7

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000496

AC:

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

Oct 11, 2024

The c.562C>T (p.R188W) alteration is located in exon 1 (coding exon 1) of the KCTD11 gene. This alteration results from a C to T substitution at nucleotide position 562, causing the arginine (R) at amino acid position 188 to be replaced by a tryptophan (W). 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

0.13

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-0.062

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.83

T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

0.55

N;.

PrimateAI

Uncertain

0.53

REVEL

Uncertain

0.29

Polyphen

1.0

D;.

MutPred

0.25

Loss of disorder (P = 0.0067);.;

MVP

0.82

MPC

1.7

ClinPred

0.29

GERP RS

2.9

Varity_R

0.096

gMVP

0.52

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over