22-37051859-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001282684.2(KCTD17):c.99G>A(p.Thr33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,475,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: KCTD17 NM_001282684.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.05

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 22-37051859-G-A is Benign according to our data. Variant chr22-37051859-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 694415.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.
• BS2: High AC in GnomAdExome at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD17	NM_001282684.2	c.99G>A	p.Thr33=	synonymous_variant	1/9	ENST00000403888.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD17	ENST00000403888.8	c.99G>A	p.Thr33=	synonymous_variant	1/9	1	NM_001282684.2	A2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152000 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000605 AC: 6 AN: 99238 Hom.: 0 AF XY: 0.0000722 AC XY: 4 AN XY: 55426

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000582

Gnomad SAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000274

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000295 AC: 39 AN: 1323912 Hom.: 0 Cov.: 32 AF XY: 0.0000459 AC XY: 30 AN XY: 653738

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000869

Gnomad4 EAS exome AF: 0.000231

Gnomad4 SAS exome AF: 0.000125

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000172

Gnomad4 OTH exome AF: 0.0000553

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152000 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74252

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000151

Asia WGS AF: 0.000580 AC: 2 AN: 3464

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Myoclonic dystonia 26 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 22, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Centre for Medical Genetics, Mumbai	Aug 14, 2019	The variant was identified in homozygous state incidentally on exome sequencing in an adult aged 20 years, neurologically normal and without family history of myoclonus or dystonia. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
Cadd	Benign	14
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: rs747826376; hg19: chr22-37447899;