Variant chr6-36474883-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173562.5(KCTD20):c.255T>G(p.Ser85Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

KCTD20
NM_173562.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.520

Variant links:

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]

KCTD20 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.072392434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD20	NM_173562.5 linkuse as main transcript	c.255T>G	p.Ser85Arg	missense_variant	3/8	ENST00000373731.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD20	ENST00000373731.7 linkuse as main transcript	c.255T>G	p.Ser85Arg	missense_variant	3/8	1	NM_173562.5	P1	Q7Z5Y7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251484

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727240

show subpopulations

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:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 27, 2022

The c.255T>G (p.S85R) alteration is located in exon 3 (coding exon 2) of the KCTD20 gene. This alteration results from a T to G substitution at nucleotide position 255, causing the serine (S) at amino acid position 85 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

0.18

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

T;.;T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.74

T;T;T;T

M_CAP

Benign

0.0094

MetaRNN

Benign

0.072

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;.;.

MutationTaster

Benign

1.0

D;D;D;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.1

N;D;D;D

REVEL

Benign

0.060

Sift

Uncertain

0.017

D;D;D;D

Sift4G

Uncertain

0.037

D;T;T;T

Polyphen

0.026

B;.;.;.

Vest4

0.17

MutPred

0.22

Loss of ubiquitination at K88 (P = 0.0304);Loss of ubiquitination at K88 (P = 0.0304);Loss of ubiquitination at K88 (P = 0.0304);Loss of ubiquitination at K88 (P = 0.0304);

MVP

0.34

MPC

0.48

ClinPred

0.15

GERP RS

2.1

Varity_R

0.098

gMVP

0.52

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over