chr11-78172809-A-C

Variant names:

• chr11-78172809-A-C
• rs230662
• NM_001029859.3:c.*963T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KCTD21	NM_001029859.3	c.*963T>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000340067.4	NP_001025030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD21	ENST00000340067.4	c.*963T>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_001029859.3	ENSP00000339340.3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.407 AC: 162 AN: 398

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.438 AC: 21 AN: 48

Other (OTH) AF: 0.750 AC: 3 AN: 4

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

African (AFR) AF: 0.279 AC: 11539 AN: 41432

American (AMR) AF: 0.477 AC: 7287 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1866 AN: 3470

East Asian (EAS) AF: 0.338 AC: 1730 AN: 5122

South Asian (SAS) AF: 0.440 AC: 2117 AN: 4816

European-Finnish (FIN) AF: 0.398 AC: 4192 AN: 10532

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32363 AN: 67938

Other (OTH) AF: 0.429 AC: 904 AN: 2106

Alfa AF: 0.461 Hom.: 31378

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
PhyloP100		-0.13
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: rs230662; hg19: chr11-77883855;