Variant 14-20429024-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001365790.2(KLHL33):c.2219G>A(p.Arg740His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000741 in 1,551,734 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00052 ( 2 hom. )

Consequence

KLHL33
NM_001365790.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.09

Variant links:

Genes affected

KLHL33 (HGNC:31952): (kelch like family member 33)

KLHL33 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00581643).

BP6

Variant 14-20429024-C-T is Benign according to our data. Variant chr14-20429024-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2644049.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KLHL33	NM_001365790.2 linkuse as main transcript	c.2219G>A	p.Arg740His	missense_variant	5/5	ENST00000636854.3
KLHL33	NM_001109997.3 linkuse as main transcript	c.1427G>A	p.Arg476His	missense_variant	4/4
KLHL33	XM_011536450.3 linkuse as main transcript	c.2219G>A	p.Arg740His	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
KLHL33	ENST00000636854.3 linkuse as main transcript	c.2219G>A	p.Arg740His	missense_variant	5/5	5	NM_001365790.2	P1
KLHL33	ENST00000344581.4 linkuse as main transcript	c.1427G>A	p.Arg476His	missense_variant	4/4	5
KLHL33	ENST00000637228.1 linkuse as main transcript	c.*378G>A		3_prime_UTR_variant	4/4	5

Frequencies

GnomAD3 genomes

AF:

0.00273

AC:

415

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00851

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.000854

AC:

133

AN:

155668

Hom.:

AF XY:

0.000727

AC XY:

AN XY:

82566

show subpopulations

Gnomad AFR exome

AF:

0.00897

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.000472

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000878

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000449

Gnomad OTH exome

AF:

0.000915

GnomAD4 exome

AF:

0.000525

AC:

734

AN:

1399388

Hom.:

Cov.:

AF XY:

0.000507

AC XY:

350

AN XY:

690200

show subpopulations

Gnomad4 AFR exome

AF:

0.00997

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.000477

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000252

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.00273

AC:

416

AN:

152346

Hom.:

Cov.:

AF XY:

0.00260

AC XY:

194

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00851

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.000858

Hom.:

Bravo

AF:

0.00326

ESP6500AA

AF:

0.0130

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.00106

AC:

Asia WGS

AF:

0.00202

AC:

AN:

3478

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

Jul 01, 2022

KLHL33: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.010

T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.72

T;T

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

Polyphen

0.85

.;P

Vest4

0.084

MVP

0.081

ClinPred

0.0080

GERP RS

1.3

Varity_R

0.031

gMVP

0.39

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