Variant X-117945517-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001168302.2(KLHL13):c.109G>A(p.Gly37Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,206,469 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 38 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.00011 ( 0 hom. 35 hem. )

Consequence

KLHL13
NM_001168302.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.22

Variant links:

Genes affected

KLHL13 (HGNC:22931): (kelch like family member 13) This gene encodes a BTB and kelch domain containing protein and belongs to the kelch repeat domain containing superfamily of proteins. The encoded protein functions as an adaptor protein that complexes with Cullin 3 and other proteins to form the Cullin 3-based E3 ubiquitin-protein ligase complex. This complex is necessary for proper chromosome segregation and completion of cytokinesis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

KLHL13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.37525967).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLHL13	NM_001168302.2 linkuse as main transcript	c.109G>A	p.Gly37Ser	missense_variant	3/8	ENST00000540167.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLHL13	ENST00000540167.6 linkuse as main transcript	c.109G>A	p.Gly37Ser	missense_variant	3/8	2	NM_001168302.2		Q9P2N7-3

Frequencies

GnomAD3 genomes

AF:

0.0000631

AC:

AN:

110979

Hom.:

Cov.:

AF XY:

0.0000903

AC XY:

AN XY:

33223

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

182602

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

67230

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:

0.0000368

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000110

AC:

121

AN:

1095490

Hom.:

Cov.:

AF XY:

0.0000970

AC XY:

AN XY:

360992

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

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:

0.000142

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000631

AC:

AN:

110979

Hom.:

Cov.:

AF XY:

0.0000903

AC XY:

AN XY:

33223

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

.;.;.;T;.;.;.;.;.

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

.;.;D;D;D;.;D;D;D

M_CAP

Pathogenic

0.39

MetaRNN

Benign

0.38

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.90

.;.;.;L;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.79

N;N;N;N;N;N;N;.;.

REVEL

Benign

0.24

Sift

Pathogenic

0.0

D;D;D;T;T;T;T;.;.

Sift4G

Benign

0.61

T;T;T;T;T;T;T;.;.

Polyphen

0.26, 0.75, 1.0

.;.;.;B;.;P;P;D;.

Vest4

0.62

MVP

0.78

ClinPred

0.62

GERP RS

5.1

Varity_R

0.28

gMVP

0.24

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over