22-37051980-C-T

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.189+31C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000865 in 1,396,012 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (4 hom., cov: 31)
  • Exomes 𝑓: 0.00053 (7 hom.)
• Consequence: KCTD17 NM_001282684.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0990

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=-0.59).
• BP6: Variant 22-37051980-C-T is Benign according to our data. Variant chr22-37051980-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1712159.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 547 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD17	NM_001282684.2	c.189+31C>T		intron_variant		ENST00000403888.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD17	ENST00000403888.8	c.189+31C>T		intron_variant		1	NM_001282684.2	A2

Frequencies

GnomAD3 genomes AF: 0.00361 AC: 547 AN: 151706 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00176

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.000425 AC: 25 AN: 58760 Hom.: 0 AF XY: 0.000328 AC XY: 11 AN XY: 33566

Gnomad AFR exome AF: 0.0145

Gnomad AMR exome AF: 0.000328

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000588

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000478

Gnomad OTH exome AF: 0.00109

GnomAD4 exome AF: 0.000531 AC: 661 AN: 1244198 Hom.: 7 Cov.: 32 AF XY: 0.000478 AC XY: 291 AN XY: 608490

Gnomad4 AFR exome AF: 0.0144

Gnomad4 AMR exome AF: 0.000516

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00713

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000317

Gnomad4 NFE exome AF: 0.0000320

Gnomad4 OTH exome AF: 0.000913

GnomAD4 genome AF: 0.00360 AC: 547 AN: 151814 Hom.: 4 Cov.: 31 AF XY: 0.00340 AC XY: 252 AN XY: 74204

Gnomad4 AFR AF: 0.0126

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00176

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000295

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00180 Hom.: 0

Bravo AF: 0.00364

Asia WGS AF: 0.00202 AC: 7 AN: 3470

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 19, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	9.8
Dann	Uncertain	0.98

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: rs200219289; hg19: chr22-37448020;