rs80062567

Variant names:

• chr11-78173865-G-A
• rs80062567
• NM_001029859.3:c.690C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001029859.3(KCTD21):​c.690C>T​(p.Ile230Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,614,148 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0077 (13 hom., cov: 31)
  • Exomes 𝑓: 0.0011 (11 hom.)
• Consequence: KCTD21 NM_001029859.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.25
• Publications: 3 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-78173865-G-A is Benign according to our data. Variant chr11-78173865-G-A is described in ClinVar as Benign. ClinVar VariationId is 778440.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.25 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00767 (1168/152268) while in subpopulation AFR AF = 0.0225 (935/41544). AF 95% confidence interval is 0.0213. There are 13 homozygotes in GnomAd4. There are 565 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029859.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD21	NM_001029859.3	MANE Select	c.690C>T	p.Ile230Ile	synonymous	Exon 2 of 2	NP_001025030.1	Q4G0X4
	KCTD21-AS1	NR_102280.1		n.971G>A		non_coding_transcript_exon	Exon 4 of 4
	KCTD21-AS1	NR_102281.1		n.443G>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD21	ENST00000340067.4	TSL:1 MANE Select	c.690C>T	p.Ile230Ile	synonymous	Exon 2 of 2	ENSP00000339340.3	Q4G0X4
	KCTD21	ENST00000908679.1		c.690C>T	p.Ile230Ile	synonymous	Exon 3 of 3	ENSP00000578738.1
	KCTD21	ENST00000908680.1		c.690C>T	p.Ile230Ile	synonymous	Exon 2 of 2	ENSP00000578739.1

Frequencies

GnomAD3 genomes AF: 0.00765 AC: 1164 AN: 152150 Hom.: 13 Cov.: 31

Gnomad AFR AF: 0.0225

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00357 AC: 898 AN: 251412 AF XY: 0.00271

Gnomad AFR exome AF: 0.0214

Gnomad AMR exome AF: 0.0144

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00141

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000880

Gnomad OTH exome AF: 0.00195

GnomAD4 exome AF: 0.00112 AC: 1633 AN: 1461880 Hom.: 11 Cov.: 32 AF XY: 0.000993 AC XY: 722 AN XY: 727242

African (AFR) AF: 0.0228 AC: 762 AN: 33480

American (AMR) AF: 0.0138 AC: 615 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00116 AC: 46 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.0000728 AC: 81 AN: 1112002

Other (OTH) AF: 0.00187 AC: 113 AN: 60396

GnomAD4 genome AF: 0.00767 AC: 1168 AN: 152268 Hom.: 13 Cov.: 31 AF XY: 0.00759 AC XY: 565 AN XY: 74458

African (AFR) AF: 0.0225 AC: 935 AN: 41544

American (AMR) AF: 0.0136 AC: 208 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68026

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00560 Hom.: 9

Bravo AF: 0.00883

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.66
DANN	Benign	0.75
PhyloP100		-3.2
Mutation Taster		=99/1	polymorphism

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: rs80062567; hg19: chr11-77884911;