6-36479645-C-A

Variant names:

• chr6-36479645-C-A
• rs1776180702
• NM_173562.5:c.592C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_173562.5(KCTD20):​c.592C>A​(p.Leu198Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCTD20 NM_173562.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.91

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.769

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD20	NM_173562.5	c.592C>A	p.Leu198Ile	missense_variant	Exon 5 of 8	ENST00000373731.7	NP_775833.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD20	ENST00000373731.7	c.592C>A	p.Leu198Ile	missense_variant	Exon 5 of 8	1	NM_173562.5	ENSP00000362836.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1453622 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723774

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.592C>A (p.L198I) alteration is located in exon 5 (coding exon 4) of the KCTD20 gene. This alteration results from a C to A substitution at nucleotide position 592, causing the leucine (L) at amino acid position 198 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Pathogenic	0.30	D
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Pathogenic	0.94	D
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.7	N;N
REVEL	Uncertain	0.61
Sift	Benign	0.032	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.91	P;.
Vest4		0.79
MutPred		0.56		Loss of catalytic residue at L198 (P = 0.0075);.;
MVP		0.95
MPC		1.3
ClinPred		0.90	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.46

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: rs1776180702; hg19: chr6-36447422;