chr22-37054720-T-G

Position:

• chr22-37054720-T-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD17	NM_001282684.2	c.298+1512T>G		intron_variant		ENST00000403888.8	NP_001269613.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD17	ENST00000403888.8	c.298+1512T>G		intron_variant		1	NM_001282684.2	ENSP00000385096	A2

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

Gnomad4 AFR AF: 0.982

Gnomad4 AMR AF: 0.948

Gnomad4 ASJ AF: 0.906

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.971

Gnomad4 FIN AF: 0.886

Gnomad4 NFE AF: 0.893

Gnomad4 OTH AF: 0.943

Alfa AF: 0.907 Hom.: 76613

Bravo AF: 0.937

Asia WGS AF: 0.986 AC: 3428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.18
DANN	Benign	0.58

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: rs710183; hg19: chr22-37450760;