rs2146333

Variant names:

• chr6-36489241-C-A
• rs2146333
• NM_173562.5:c.*2066C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KCTD20	NM_173562.5	c.*2066C>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000373731.7	NP_775833.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD20	ENST00000373731.7	c.*2066C>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_173562.5	ENSP00000362836.2
KCTD20	ENST00000449081.6	c.*2066C>A		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000412205.2
KCTD20	ENST00000536244.5	c.*2066C>A		3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000439118.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.237 AC: 94 AN: 396

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.125 AC: 1 AN: 8

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.418 AC: 17298 AN: 41424

American (AMR) AF: 0.247 AC: 3770 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 764 AN: 3464

East Asian (EAS) AF: 0.389 AC: 2013 AN: 5174

South Asian (SAS) AF: 0.210 AC: 1015 AN: 4824

European-Finnish (FIN) AF: 0.244 AC: 2573 AN: 10556

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 13004 AN: 68004

Other (OTH) AF: 0.264 AC: 558 AN: 2110

Alfa AF: 0.220 Hom.: 5264

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
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2146333; hg19: chr6-36457018;