rs230662

Positions:

• chr11-78172809-A-C

Variant summary

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

The NM_001029859.3(KCTD21):​c.*963T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,338 control chromosomes in the GnomAD database, including 13,611 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 0.41 (13570 hom., cov: 31)
  • Exomes 𝑓: 0.42 (41 hom.)
• Consequence: KCTD21 NM_001029859.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

Genes affected

KCTD21 (HGNC:27452): (potassium channel tetramerization domain containing 21) Enables cullin family protein binding activity; histone deacetylase binding activity; and identical protein binding activity. Involved in negative regulation of smoothened signaling pathway and ubiquitin-dependent protein catabolic process. [provided by Alliance of Genome Resources, Apr 2022]

KCTD21-AS1 (HGNC:48674): (KCTD21 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD21	NM_001029859.3	c.*963T>G		3_prime_UTR_variant	2/2	ENST00000340067.4
KCTD21-AS1	NR_102280.1	n.506-591A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD21	ENST00000340067.4	c.*963T>G		3_prime_UTR_variant	2/2	1	NM_001029859.3	P1
KCTD21-AS1	ENST00000662186.1	n.408-591A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62589 AN: 151766 Hom.: 13562 Cov.: 31

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.431

GnomAD4 exome AF: 0.416 AC: 189 AN: 454 Hom.: 41 Cov.: 0 AF XY: 0.400 AC XY: 112 AN XY: 280

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.407

Gnomad4 NFE exome AF: 0.438

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.412 AC: 62630 AN: 151884 Hom.: 13570 Cov.: 31 AF XY: 0.409 AC XY: 30323 AN XY: 74208

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.429

Alfa AF: 0.467 Hom.: 23360

Bravo AF: 0.416

Asia WGS AF: 0.380 AC: 1321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.39

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: rs230662; hg19: chr11-77883855;