Variant chr17-7353535-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001363642.1(KCTD11):c.710A>T(p.Glu237Val) variant causes a missense change. The variant allele was found at a frequency of 0.000026 in 1,575,078 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

KCTD11
NM_001363642.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.77

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD11	NM_001363642.1 linkuse as main transcript	c.710A>T	p.Glu237Val	missense_variant	1/1	ENST00000333751.8
KCTD11	NM_001002914.3 linkuse as main transcript	c.593A>T	p.Glu198Val	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD11	ENST00000333751.8 linkuse as main transcript	c.710A>T	p.Glu237Val	missense_variant	1/1		NM_001363642.1		Q693B1-2
	ENST00000572417.1 linkuse as main transcript	n.276-703T>A		intron_variant, non_coding_transcript_variant		2
KCTD11	ENST00000576980.2 linkuse as main transcript	c.593A>T	p.Glu198Val	missense_variant	1/1			P1	Q693B1-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152102

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000638

AC:

AN:

219272

Hom.:

AF XY:

0.0000758

AC XY:

AN XY:

118664

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000646

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000121

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1422976

Hom.:

Cov.:

AF XY:

0.0000327

AC XY:

AN XY:

703378

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000484

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:

0.0000312

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74288

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000661

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

Jul 27, 2022

The c.593A>T (p.E198V) alteration is located in exon 1 (coding exon 1) of the KCTD11 gene. This alteration results from a A to T substitution at nucleotide position 593, causing the glutamic acid (E) at amino acid position 198 to be replaced by a valine (V). 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

Pathogenic

0.78

BayesDel_addAF

Uncertain

0.092

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

T;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.68

T;T

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Uncertain

-0.12

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.71

Polyphen

1.0

D;.

MVP

0.91

MPC

1.8

ClinPred

0.44

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.13

gMVP

0.72

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