chr22-37062565-C-G

Position:

• chr22-37062565-C-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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. 14/20 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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.10

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
KCTD17	NM_001282684.2	c.916C>G	p.His306Asp	missense_variant	9/9	ENST00000403888.8	NP_001269613.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00149 AC: 227 AN: 152074 Hom.: 2 Cov.: 32

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

GnomAD3 exomes AF: 0.00138 AC: 346 AN: 250054 Hom.: 0 AF XY: 0.00151 AC XY: 205 AN XY: 135406

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 SAS exome AF: 0.000982

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.: 10 Cov.: 35 AF XY: 0.00268 AC XY: 1951 AN XY: 726904

Gnomad4 AFR exome AF: 0.000538

Gnomad4 AMR exome AF: 0.000716

Gnomad4 ASJ exome AF: 0.000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00101

Gnomad4 FIN exome AF: 0.000337

Gnomad4 NFE exome AF: 0.00338

Gnomad4 OTH exome AF: 0.00161

GnomAD4 genome AF: 0.00149 AC: 227 AN: 152192 Hom.: 2 Cov.: 32 AF XY: 0.00130 AC XY: 97 AN XY: 74414

Gnomad4 AFR AF: 0.000819

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000661

Gnomad4 NFE AF: 0.00251

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00162 Hom.: 0

Bravo AF: 0.00145

TwinsUK AF: 0.00378 AC: 14

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00209 AC: 18

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

Submissions by phenotype

KCTD17-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 25, 2020

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

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

KCTD17: BP4, BS1 -

Myoclonic dystonia 26 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 18, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0055	.;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.074
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.0099	T;T
MetaSVM	Benign	-0.96	T
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.91	N;N
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.014	D;D
Polyphen		0.065	B;B
Vest4		0.34
MVP		0.63
MPC		0.13
ClinPred		0.023	T
GERP RS		3.8
Varity_R		0.21
gMVP		0.41

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

Other links and lift over

dbSNP: rs146711968; hg19: chr22-37458605; COSMIC: COSV99061793; COSMIC: COSV99061793;