Variant 22-37051746-A-C 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.-15A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 1,216,594 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 0.000013 ( 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: 0.675

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=0.12167245).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD17	NM_001282684.2 linkuse as main transcript	c.-15A>C		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.-15A>C	5_prime_UTR_variant	1/9	1	NM_001282684.2	ENSP00000385096.4	Q8N5Z5
KCTD17	ENST00000402077.8 linkuse as main transcript	c.-15A>C	5_prime_UTR_variant	1/8	1		ENSP00000384391.4	Q8N5Z5
KCTD17	ENST00000610767.5 linkuse as main transcript	c.-15A>C	upstream_gene_variant		3		ENSP00000480699.2	A0A087WX35

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151700

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000563

AC:

AN:

1064894

Hom.:

Cov.:

AF XY:

0.00000596

AC XY:

AN XY:

503728

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000549

Gnomad4 OTH exome

AF:

0.0000237

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151700

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74114

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000295

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2022

The c.7A>C (p.T3P) alteration is located in exon 1 (coding exon 1) of the KCTD17 gene. This alteration results from a A to C substitution at nucleotide position 7, causing the threonine (T) at amino acid position 3 to be replaced by a proline (P). 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

0.098

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0068

T;.;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.46

T;T;T

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.99

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.25

.;N;N

REVEL

Benign

0.056

Sift

Uncertain

0.0020

.;D;D

Sift4G

Uncertain

0.040

D;D;D

Polyphen

0.0

.;B;.

Vest4

0.15

MutPred

0.30

Loss of phosphorylation at T3 (P = 9e-04);Loss of phosphorylation at T3 (P = 9e-04);Loss of phosphorylation at T3 (P = 9e-04);

MVP

0.26

MPC

2.3

ClinPred

0.79

GERP RS

3.0

Varity_R

0.18

gMVP

0.30

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