chr22-37051815-G-A

Position:

chr22-37051815-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001282684.2(KCTD17):c.55G>A(p.Ala19Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,284,934 control chromosomes in the GnomAD database, including 10,098 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1092 hom., cov: 31)

Exomes 𝑓: 0.12 ( 9006 hom. )

Consequence

KCTD17
NM_001282684.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.745

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011972487).

BP6

Variant 22-37051815-G-A is Benign according to our data. Variant chr22-37051815-G-A is described in ClinVar as [Benign]. Clinvar id is 1168447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD17	NM_001282684.2 linkuse as main transcript	c.55G>A	p.Ala19Thr	missense_variant	1/9	ENST00000403888.8	NP_001269613.2	Q8N5Z5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KCTD17	ENST00000403888.8 linkuse as main transcript	c.55G>A	p.Ala19Thr	missense_variant	1/9	1	NM_001282684.2	ENSP00000385096.4	Q8N5Z5
KCTD17	ENST00000402077.8 linkuse as main transcript	c.55G>A	p.Ala19Thr	missense_variant	1/8	1		ENSP00000384391.4	Q8N5Z5
KCTD17	ENST00000610767.5 linkuse as main transcript	c.55G>A	p.Ala19Thr	missense_variant	1/6	3		ENSP00000480699.2	A0A087WX35
KCTD17	ENST00000421900.5 linkuse as main transcript	n.-39G>A		upstream_gene_variant		5		ENSP00000409116.1	H7C323

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17519

AN:

151616

Hom.:

1092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.0857

Gnomad AMR

AF:

0.0767

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.00271

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.0417

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.102

GnomAD3 exomes

AF:

0.108

AC:

2472

AN:

22988

Hom.:

196

AF XY:

0.108

AC XY:

1628

AN XY:

15018

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.0685

Gnomad ASJ exome

AF:

0.0842

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.133

Gnomad NFE exome

AF:

0.118

Gnomad OTH exome

AF:

0.0923

GnomAD4 exome

AF:

0.123

AC:

139051

AN:

1133208

Hom.:

9006

Cov.:

AF XY:

0.123

AC XY:

66996

AN XY:

546408

show subpopulations

Gnomad4 AFR exome

AF:

0.113

Gnomad4 AMR exome

AF:

0.0623

Gnomad4 ASJ exome

AF:

0.100

Gnomad4 EAS exome

AF:

0.00109

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.157

Gnomad4 NFE exome

AF:

0.128

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.116

AC:

17538

AN:

151726

Hom.:

1092

Cov.:

AF XY:

0.115

AC XY:

8504

AN XY:

74162

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.0766

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.00272

Gnomad4 SAS

AF:

0.103

Gnomad4 FIN

AF:

0.146

Gnomad4 NFE

AF:

0.129

Gnomad4 OTH

AF:

0.101

Alfa

AF:

0.124

Hom.:

158

Bravo

AF:

0.109

ExAC

AF:

0.0437

AC:

994

Asia WGS

AF:

0.0640

AC:

222

AN:

3454

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 15, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

KCTD17-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 19, 2019

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

Myoclonic dystonia 26

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0066

T;.;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.66

T;T;T

MetaRNN

Benign

0.0012

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

.;N;N

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.18

.;N;N

REVEL

Benign

0.016

Sift

Benign

0.21

.;T;T

Sift4G

Benign

0.59

T;T;T

Polyphen

0.27, 0.18

.;B;B

Vest4

0.061

MPC

2.0

ClinPred

0.014

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.069

gMVP

0.14

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