rs149432408

chr22-37056417-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001282684.2(KCTD17):c.390+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,612,104 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (1 hom.)
• Consequence: KCTD17 NM_001282684.2 splice_donor_region, intron
• Scores: Splicing: ADA: 0.00003988
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.40

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 22-37056417-G-A is Benign according to our data. Variant chr22-37056417-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 542657.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 162 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD17	NM_001282684.2	c.390+6G>A		splice_donor_region_variant, intron_variant		ENST00000403888.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD17	ENST00000403888.8	c.390+6G>A		splice_donor_region_variant, intron_variant		1	NM_001282684.2	A2

Frequencies

GnomAD3 genomes AF: 0.00106 AC: 162 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00216

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00169

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000862 AC: 215 AN: 249390 Hom.: 0 AF XY: 0.000830 AC XY: 112 AN XY: 134868

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.000643

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00204

Gnomad NFE exome AF: 0.00123

Gnomad OTH exome AF: 0.000825

GnomAD4 exome AF: 0.00170 AC: 2477 AN: 1459782 Hom.: 1 Cov.: 29 AF XY: 0.00166 AC XY: 1208 AN XY: 726166

Gnomad4 AFR exome AF: 0.000389

Gnomad4 AMR exome AF: 0.000673

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00157

Gnomad4 NFE exome AF: 0.00206

Gnomad4 OTH exome AF: 0.00103

GnomAD4 genome AF: 0.00106 AC: 162 AN: 152322 Hom.: 0 Cov.: 32 AF XY: 0.000967 AC XY: 72 AN XY: 74480

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00216

Gnomad4 NFE AF: 0.00169

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00111 Hom.: 0

Bravo AF: 0.000922

EpiCase AF: 0.00142

EpiControl AF: 0.00160

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Myoclonic dystonia 26 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 27, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	12
Dann	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000040
dbscSNV1_RF	Benign	0.0
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: rs149432408; hg19: chr22-37452457;