NM_001282684.2:c.298+1512T>G

Variant names:

• chr22-37054720-T-G
• rs710183
• NM_001282684.2:c.298+1512T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282684.2(KCTD17):​c.298+1512T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.93 in 152,234 control chromosomes in the GnomAD database, including 65,985 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.93 (65985 hom., cov: 32)
• Consequence: KCTD17 NM_001282684.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

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.298+1512T>G		intron	N/A	NP_001269613.2
	KCTD17	NM_024681.4		c.298+1512T>G		intron	N/A	NP_078957.3
	KCTD17	NM_001282685.2		c.298+1512T>G		intron	N/A	NP_001269614.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD17	ENST00000403888.8	TSL:1 MANE Select	c.298+1512T>G		intron	N/A	ENSP00000385096.4
	KCTD17	ENST00000402077.8	TSL:1	c.298+1512T>G		intron	N/A	ENSP00000384391.4
	KCTD17	ENST00000610767.5	TSL:3	c.298+1512T>G		intron	N/A	ENSP00000480699.2

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141446 AN: 152116 Hom.: 65922 Cov.: 32

Gnomad AFR AF: 0.982

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.942

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.930 AC: 141569 AN: 152234 Hom.: 65985 Cov.: 32 AF XY: 0.931 AC XY: 69333 AN XY: 74432

African (AFR) AF: 0.982 AC: 40798 AN: 41540

American (AMR) AF: 0.948 AC: 14508 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3145 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5161 AN: 5162

South Asian (SAS) AF: 0.971 AC: 4688 AN: 4828

European-Finnish (FIN) AF: 0.886 AC: 9404 AN: 10618

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.893 AC: 60739 AN: 67996

Other (OTH) AF: 0.943 AC: 1987 AN: 2108

Alfa AF: 0.909 Hom.: 99258

Bravo AF: 0.937

Asia WGS AF: 0.986 AC: 3428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.18
DANN	Benign	0.58
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs710183; hg19: chr22-37450760;