chr22-37059395-G-A

Variant names:

• chr22-37059395-G-A
• rs144682183
• NM_001282684.2:c.569G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001282684.2(KCTD17):​c.569G>A​(p.Ser190Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,460,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. S190T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: KCTD17 NM_001282684.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.049948126).
• BS2: High AC in GnomAdExome4 at 13 AD gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD17	NM_001282684.2	MANE Select	c.569G>A	p.Ser190Asn	missense	Exon 5 of 9	NP_001269613.2
	KCTD17	NM_024681.4		c.569G>A	p.Ser190Asn	missense	Exon 5 of 8	NP_078957.3
	KCTD17	NM_001282685.2		c.569G>A	p.Ser190Asn	missense	Exon 5 of 7	NP_001269614.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD17	ENST00000403888.8	TSL:1 MANE Select	c.569G>A	p.Ser190Asn	missense	Exon 5 of 9	ENSP00000385096.4
	KCTD17	ENST00000402077.8	TSL:1	c.569G>A	p.Ser190Asn	missense	Exon 5 of 8	ENSP00000384391.4
	KCTD17	ENST00000610767.5	TSL:3	c.569G>A	p.Ser190Asn	missense	Exon 5 of 6	ENSP00000480699.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 248976 AF XY: 0.0000223

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: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1460218 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 726488

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111798

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 33

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.69
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.67
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	-0.46	N
PhyloP100		1.8
PrimateAI	Benign	0.41	T
PROVEAN	Benign	1.9	N
REVEL	Benign	0.16
Sift	Benign	0.77	T
Sift4G	Benign	1.0	T
Polyphen		0.0070	B
Vest4		0.046
MutPred		0.20		Gain of sheet (P = 0.0221)
MVP		0.65
MPC		0.085
ClinPred		0.026	T
GERP RS		1.8
Varity_R		0.019
gMVP		0.072
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs144682183; hg19: chr22-37455435;