6-36470149-A-G

Variant names:

• chr6-36470149-A-G
• rs376919640
• NM_173562.5:c.52A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173562.5(KCTD20):​c.52A>G​(p.Ser18Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCTD20 NM_173562.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15893811).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173562.5. 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
	KCTD20	NM_173562.5	MANE Select	c.52A>G	p.Ser18Gly	missense	Exon 2 of 8	NP_775833.2
	KCTD20	NM_001286579.2		c.52A>G	p.Ser18Gly	missense	Exon 2 of 5	NP_001273508.1	Q7Z5Y7-2
	KCTD20	NM_001286580.2		c.-110A>G		5_prime_UTR	Exon 2 of 7	NP_001273509.1	Q7Z5Y7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD20	ENST00000373731.7	TSL:1 MANE Select	c.52A>G	p.Ser18Gly	missense	Exon 2 of 8	ENSP00000362836.2	Q7Z5Y7-1
	KCTD20	ENST00000449081.6	TSL:1	c.52A>G	p.Ser18Gly	missense	Exon 2 of 5	ENSP00000412205.2	Q7Z5Y7-2
	KCTD20	ENST00000901245.1		c.52A>G	p.Ser18Gly	missense	Exon 4 of 10	ENSP00000571304.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251376 AF XY: 0.00

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.061
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.7
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.043
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.057	T
Polyphen		0.043	B
Vest4		0.096
MVP		0.47
MPC		0.37
ClinPred		0.43	T
GERP RS		4.2
Varity_R		0.20
gMVP		0.42
Mutation Taster		=90/10	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: rs376919640; hg19: chr6-36437926;