Genetic Variant KCTD17:p.His306Asn (chr22-37062565-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001282684.2(KCTD17):c.916C>A(p.His306Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H306D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCTD17
NM_001282684.2 missense

Scores

Clinical Significance

Not reported in ClinVar

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

KCTD17 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08762717).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282684.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCTD17	NM_001282684.2	MANE Select	c.916C>A	p.His306Asn	missense	Exon 9 of 9	NP_001269613.2	Q8N5Z5-1
KCTD17	NM_024681.4		c.844C>A	p.His282Asn	missense	Exon 8 of 8	NP_078957.3	Q8N5Z5-2
KCTD17	NM_001282685.2		c.*87C>A		3_prime_UTR	Exon 7 of 7	NP_001269614.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCTD17	ENST00000403888.8	TSL:1 MANE Select	c.916C>A	p.His306Asn	missense	Exon 9 of 9	ENSP00000385096.4	Q8N5Z5-1
KCTD17	ENST00000402077.8	TSL:1	c.844C>A	p.His282Asn	missense	Exon 8 of 8	ENSP00000384391.4	Q8N5Z5-2
KCTD17	ENST00000851347.1		c.898C>A	p.His300Asn	missense	Exon 8 of 8	ENSP00000521406.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

250054

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461308

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726906

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5630

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111758

Other (OTH)

AF:

0.00

AC:

AN:

60342

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0055

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.074

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.58

M_CAP

Benign

0.066

MetaRNN

Benign

0.088

MetaSVM

Benign

-0.96

PhyloP100

1.1

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.70

REVEL

Benign

0.042

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.015

Polyphen

0.065

Vest4

0.16

MutPred

0.19

Gain of loop (P = 0.069)

MVP

0.60

MPC

0.11

ClinPred

0.54

GERP RS

3.8

Varity_R

0.15

gMVP

0.26

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over