Variant 22-37051750-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001282684.2(KCTD17):c.-11C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000172 in 1,218,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

KCTD17
NM_001282684.2 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0300

Variant links:

Genes affected

KCTD17 (HGNC:25705): (potassium channel tetramerization domain containing 17) This gene encodes a protein that belongs to a conserved family of potassium channel tetramerization domain (KCTD)-containing proteins. The encoded protein functions in ciliogenesis by acting as a substrate adaptor for the cullin3-based ubiquitin-conjugating enzyme E3 ligase, and targets trichoplein, a keratin-binding protein, for degradation via polyubiquitinylation. A mutation in this gene is associated with autosomal dominant myoclonic dystonia 26. [provided by RefSeq, Nov 2016]

KCTD17 links:

KCTD17 (HGNC:):

KCTD17 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.076214224).

BS2

High AC in GnomAd4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD17	NM_001282684.2 linkuse as main transcript	c.-11C>G		5_prime_UTR_variant	1/9	ENST00000403888.8	NP_001269613.2	Q8N5Z5

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KCTD17	ENST00000403888.8 linkuse as main transcript	c.-11C>G	5_prime_UTR_variant	1/9	1	NM_001282684.2	ENSP00000385096.4	Q8N5Z5
KCTD17	ENST00000402077.8 linkuse as main transcript	c.-11C>G	5_prime_UTR_variant	1/8	1		ENSP00000384391.4	Q8N5Z5
KCTD17	ENST00000610767.5 linkuse as main transcript	c.-11C>G	upstream_gene_variant		3		ENSP00000480699.2	A0A087WX35

Frequencies

GnomAD3 genomes

AF:

0.0000988

AC:

AN:

151812

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000562

AC:

AN:

1066834

Hom.:

Cov.:

AF XY:

0.00000792

AC XY:

AN XY:

504776

show subpopulations

Gnomad4 AFR exome

AF:

0.000226

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:

0.00

Gnomad4 OTH exome

AF:

0.0000236

GnomAD4 genome

AF:

0.0000988

AC:

AN:

151812

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74168

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000529

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Myoclonic dystonia 26

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 12, 2022

Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with KCTD17-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.05%). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 4 of the KCTD17 protein (p.Pro4Arg). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

T;.;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.73

T;T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.076

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-1.2

.;N;N

REVEL

Benign

0.025

Sift

Uncertain

0.0050

.;D;D

Sift4G

Uncertain

0.047

D;T;D

Polyphen

0.0010

.;B;.

Vest4

0.054

MutPred

0.31

Gain of MoRF binding (P = 5e-04);Gain of MoRF binding (P = 5e-04);Gain of MoRF binding (P = 5e-04);

MVP

0.26

MPC

2.4

ClinPred

0.51

GERP RS

0.53

Varity_R

0.13

gMVP

0.16

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