6-36484729-A-G

Position:

• chr6-36484729-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173562.5(KCTD20):​c.872A>G​(p.Lys291Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,228 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: KCTD20 NM_173562.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD20	NM_173562.5	c.872A>G	p.Lys291Arg	missense_variant	7/8	ENST00000373731.7	NP_775833.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD20	ENST00000373731.7	c.872A>G	p.Lys291Arg	missense_variant	7/8	1	NM_173562.5	ENSP00000362836	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1430228 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 712628

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: 9.19e-7

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

The c.872A>G (p.K291R) alteration is located in exon 7 (coding exon 6) of the KCTD20 gene. This alteration results from a A to G substitution at nucleotide position 872, causing the lysine (K) at amino acid position 291 to be replaced by an arginine (R). 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	Benign	0.12
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T;.;.
Eigen	Uncertain	0.61
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Uncertain	-0.072	T
MutationAssessor	Benign	1.6	L;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.64	N;N;N
REVEL	Uncertain	0.45
Sift	Benign	0.089	T;T;T
Sift4G	Benign	0.40	T;T;T
Polyphen		1.0	D;.;D
Vest4		0.68
MutPred		0.22		Loss of ubiquitination at K291 (P = 0.0255);.;.;
MVP		0.87
MPC		0.66
ClinPred		0.82	D
GERP RS		5.5
Varity_R		0.14
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-36452506;