Genetic Variant KLHL33:p.Arg757Gln (chr14-20428973-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001365790.2(KLHL33):c.2270G>A(p.Arg757Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000606 in 1,551,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

KLHL33
NM_001365790.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.94

Publications

0 publications found

Variant links:

Genes affected

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

KLHL33 links:

ENSG00000291038 (HGNC:):

ENSG00000291038 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2224997).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365790.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL33	NM_001365790.2	MANE Select	c.2270G>A	p.Arg757Gln	missense	Exon 5 of 5	NP_001352719.1	A0A1B0GUB7
	KLHL33	NM_001109997.3		c.1478G>A	p.Arg493Gln	missense	Exon 4 of 4	NP_001103467.2	A6NCF5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KLHL33	ENST00000636854.3	TSL:5 MANE Select	c.2270G>A	p.Arg757Gln	missense	Exon 5 of 5	ENSP00000490040.1	A0A1B0GUB7
KLHL33	ENST00000344581.4	TSL:5	c.1478G>A	p.Arg493Gln	missense	Exon 4 of 4	ENSP00000341549.4	A6NCF5
KLHL33	ENST00000637228.1	TSL:5	c.*429G>A		3_prime_UTR	Exon 4 of 4	ENSP00000489731.1	A0A1B0GTK0

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000704

AC:

AN:

156224

AF XY:

0.0000483

show subpopulations

Gnomad AFR exome

AF:

0.000505

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000497

Gnomad OTH exome

AF:

0.000228

GnomAD4 exome

AF:

0.0000536

AC:

AN:

1399398

Hom.:

Cov.:

AF XY:

0.0000507

AC XY:

AN XY:

690200

show subpopulations

African (AFR)

AF:

0.000380

AC:

AN:

31598

American (AMR)

AF:

0.000168

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.000140

AC:

AN:

35738

South Asian (SAS)

AF:

0.0000252

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49268

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0000324

AC:

AN:

1078976

Other (OTH)

AF:

0.000241

AC:

AN:

58002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000125

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41562

American (AMR)

AF:

0.000392

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000197

Hom.:

Bravo

AF:

0.000212

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000383

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0086

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.023

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.5

PhyloP100

5.9

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.60

REVEL

Benign

0.26

Sift

Uncertain

0.023

Sift4G

Uncertain

0.020

Polyphen

1.0

Vest4

0.39

MVP

0.17

ClinPred

0.094

GERP RS

5.2

Varity_R

0.20

gMVP

0.28

Mutation Taster

=76/24

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over