rs2146333

Positions:

• chr6-36489241-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173562.5(KCTD20):​c.*2066C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,452 control chromosomes in the GnomAD database, including 6,369 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 0.27 (6362 hom., cov: 32)
  • Exomes 𝑓: 0.24 (7 hom.)
• Consequence: KCTD20 NM_173562.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

Genes affected

KCTD20 (HGNC:21052): (potassium channel tetramerization domain containing 20) Predicted to enable identical protein binding activity. Predicted to be involved in positive regulation of phosphorylation. Predicted to be integral component of membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD20	NM_173562.5	c.*2066C>A		3_prime_UTR_variant	8/8	ENST00000373731.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD20	ENST00000373731.7	c.*2066C>A		3_prime_UTR_variant	8/8	1	NM_173562.5	P1
KCTD20	ENST00000449081.6	c.*2066C>A		3_prime_UTR_variant	5/5	1
KCTD20	ENST00000536244.5	c.*2066C>A		3_prime_UTR_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41151 AN: 151926 Hom.: 6347 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.263

GnomAD4 exome AF: 0.235 AC: 96 AN: 408 Hom.: 7 Cov.: 0 AF XY: 0.218 AC XY: 55 AN XY: 252

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.271 AC: 41213 AN: 152044 Hom.: 6362 Cov.: 32 AF XY: 0.271 AC XY: 20160 AN XY: 74332

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.264

Alfa AF: 0.212 Hom.: 3684

Bravo AF: 0.281

Asia WGS AF: 0.278 AC: 967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.52

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: rs2146333; hg19: chr6-36457018;