Variant 16-2682785-C-A 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_018992.4(KCTD5):c.237C>A(p.Asp79Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000938 in 1,598,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

KCTD5
NM_018992.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.500

Variant links:

Genes affected

KCTD5 (HGNC:21423): (potassium channel tetramerization domain containing 5) Enables identical protein binding activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KCTD5 links:

Genome browser will be placed here

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=0.06800565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD5	NM_018992.4 linkuse as main transcript	c.237C>A	p.Asp79Glu	missense_variant	1/6	ENST00000301738.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
KCTD5	ENST00000301738.9 linkuse as main transcript	c.237C>A	p.Asp79Glu	missense_variant	1/6	1	NM_018992.4	P1
KCTD5	ENST00000564195.1 linkuse as main transcript	c.237C>A	p.Asp79Glu	missense_variant	1/5	5
KCTD5	ENST00000564246.1 linkuse as main transcript	n.253C>A		non_coding_transcript_exon_variant	1/4	3
KCTD5	ENST00000570005.5 linkuse as main transcript	n.258C>A		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.0000386

AC:

AN:

232874

Hom.:

AF XY:

0.0000314

AC XY:

AN XY:

127310

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000189

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:

0.0000188

Gnomad OTH exome

AF:

0.000180

GnomAD4 exome

AF:

0.00000830

AC:

AN:

1446252

Hom.:

Cov.:

AF XY:

0.00000834

AC XY:

AN XY:

719344

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000162

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:

0.00000362

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000955

Bravo

AF:

0.0000869

ExAC

AF:

0.00000824

AC:

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

Jul 09, 2021

The c.237C>A (p.D79E) alteration is located in exon 1 (coding exon 1) of the KCTD5 gene. This alteration results from a C to A substitution at nucleotide position 237, causing the aspartic acid (D) at amino acid position 79 to be replaced by a glutamic acid (E). 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

0.20

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.49

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.21

T;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.068

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.015

N;.

MutationTaster

Benign

0.87

D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.61

N;N

REVEL

Benign

0.097

Sift

Benign

0.60

T;T

Sift4G

Benign

0.63

T;T

Polyphen

0.0

B;.

Vest4

0.13

MutPred

0.41

Gain of ubiquitination at K84 (P = 0.0701);Gain of ubiquitination at K84 (P = 0.0701);

MVP

0.34

MPC

0.55

ClinPred

0.032

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.18

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