22-37062565-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001282684.2(KCTD17):c.916C>G(p.His306Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00263 in 1,613,498 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 10 hom. )

Consequence

KCTD17
NM_001282684.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.10

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

myoclonic dystonia 26
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
myoclonus-dystonia syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KCTD17 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009907991).

BP6

Variant 22-37062565-C-G is Benign according to our data. Variant chr22-37062565-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 569014.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 227 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD17	NM_001282684.2 link	c.916C>G	p.His306Asp	missense_variant	Exon 9 of 9	ENST00000403888.8	NP_001269613.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
KCTD17	ENST00000403888.8 link	c.916C>G	p.His306Asp	missense_variant	Exon 9 of 9	1	NM_001282684.2	ENSP00000385096.4
KCTD17	ENST00000402077.8 link	c.844C>G	p.His282Asp	missense_variant	Exon 8 of 8	1		ENSP00000384391.4
KCTD17	ENST00000610767.5 link	c.*11C>G		3_prime_UTR_variant	Exon 6 of 6	3		ENSP00000480699.2
KCTD17	ENST00000456470.1 link	c.*87C>G		3_prime_UTR_variant	Exon 7 of 7	3		ENSP00000409638.1

Frequencies

GnomAD3 genomes

AF:

0.00149

AC:

227

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000661

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00251

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00138

AC:

346

AN:

250054

AF XY:

0.00151

show subpopulations

Gnomad AFR exome

AF:

0.000495

Gnomad AMR exome

AF:

0.000696

Gnomad ASJ exome

AF:

0.000499

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00236

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00275

AC:

4020

AN:

1461306

Hom.:

Cov.:

AF XY:

0.00268

AC XY:

1951

AN XY:

726904

show subpopulations

African (AFR)

AF:

0.000538

AC:

AN:

33476

American (AMR)

AF:

0.000716

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.000383

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00101

AC:

AN:

86198

European-Finnish (FIN)

AF:

0.000337

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5630

European-Non Finnish (NFE)

AF:

0.00338

AC:

3758

AN:

1111756

Other (OTH)

AF:

0.00161

AC:

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

222

444

667

889

1111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

150

300

450

600

750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00149

AC:

227

AN:

152192

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.000819

AC:

AN:

41524

American (AMR)

AF:

0.000654

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000661

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00251

AC:

171

AN:

68000

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00162

Hom.:

Bravo

AF:

0.00145

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00144

AC:

175

EpiCase

AF:

0.00234

EpiControl

AF:

0.00255

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

KCTD17-related disorder

Benign:1

Feb 25, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

not provided

Benign:1

Oct 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KCTD17: BP4, BS1

Myoclonic dystonia 26

Benign:1

Oct 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0

.;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.074

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.56

T;T

M_CAP

Benign

0.079

MetaRNN

Benign

0.0099

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

.;.

PhyloP100

1.1

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.91

N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.014

D;D

Vest4

0.34

ClinPred

0.023

GERP RS

3.8

Varity_R

0.21

gMVP

0.41

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over