rs144682183

Positions:

• chr22-37059395-G-A
• chr22-37059395-G-C

Variant summary

Our verdict is Benign. Variant got -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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 -8 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD17	NM_001282684.2	c.569G>A	p.Ser190Asn	missense_variant	5/9	ENST00000403888.8	NP_001269613.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD17	ENST00000403888.8	c.569G>A	p.Ser190Asn	missense_variant	5/9	1	NM_001282684.2	ENSP00000385096	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 248976 Hom.: 0 AF XY: 0.0000223 AC XY: 3 AN XY: 134752

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 SAS 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

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000989

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.67
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.050	T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	-0.46	.;N;N
MutationTaster	Benign	0.76	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	1.9	.;N;N
REVEL	Benign	0.16
Sift	Benign	0.77	.;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0070, 0.0010	.;B;B
Vest4		0.046
MutPred		0.20		Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);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

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: rs144682183; hg19: chr22-37455435;