Variant X-118028424-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001168302.2(KLHL13):c.50G>A(p.Arg17Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000426 in 1,104,285 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000046 ( 0 hom. 13 hem. )

Consequence

KLHL13
NM_001168302.2 missense, splice_region

Scores

Splicing: ADA: 0.7614

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.03

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12793481).

BP6

Variant X-118028424-C-T is Benign according to our data. Variant chrX-118028424-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661260.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KLHL13	NM_001168302.2 linkuse as main transcript	c.50G>A	p.Arg17Gln	missense_variant, splice_region_variant	2/8	ENST00000540167.6
KLHL13	NM_001168301.2 linkuse as main transcript	c.50G>A	p.Arg17Gln	missense_variant, splice_region_variant	2/8
KLHL13	NM_001168303.4 linkuse as main transcript	c.-55-82849G>A		intron_variant
KLHL13	NM_001394866.1 linkuse as main transcript	c.-28-82849G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	UniProt
KLHL13	ENST00000540167.6 linkuse as main transcript	c.50G>A	p.Arg17Gln	missense_variant, splice_region_variant	2/8	2	NM_001168302.2	Q9P2N7-3
KLHL13	ENST00000371882.5 linkuse as main transcript	c.-28-82849G>A		intron_variant		1		Q9P2N7-2
KLHL13	ENST00000541812.5 linkuse as main transcript	c.50G>A	p.Arg17Gln	missense_variant, splice_region_variant	2/8	2		Q9P2N7-3
KLHL13	ENST00000453826.1 linkuse as main transcript	c.50G>A	p.Arg17Gln	missense_variant, splice_region_variant	1/4	5

Frequencies

GnomAD3 genomes

AF:

0.00000901

AC:

AN:

110935

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33255

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000593

AC:

AN:

101230

Hom.:

AF XY:

0.0000819

AC XY:

AN XY:

36630

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:

0.000214

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000736

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000463

AC:

AN:

993350

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

305074

show subpopulations

Gnomad4 AFR exome

AF:

0.0000418

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000312

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000374

Gnomad4 OTH exome

AF:

0.0000235

GnomAD4 genome

AF:

0.00000901

AC:

AN:

110935

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33255

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:

0.0000189

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.000157

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

KLHL13: PP3, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Uncertain

1.0

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.54

.;T;T

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

D;D;N;N

PROVEAN

Benign

0.11

N;N;.

REVEL

Benign

0.056

Sift

Uncertain

0.016

D;D;.

Sift4G

Benign

0.26

T;T;.

Polyphen

0.27

B;B;.

Vest4

0.14

MutPred

0.29

Loss of MoRF binding (P = 0.0794);Loss of MoRF binding (P = 0.0794);Loss of MoRF binding (P = 0.0794);

MVP

0.78

ClinPred

0.12

GERP RS

4.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.76

dbscSNV1_RF

Benign

0.69

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