Variant rs7145318 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001365790.2(KLHL33):c.2338G>A(p.Ala780Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 1,551,436 control chromosomes in the GnomAD database, including 272,074 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.62 ( 29766 hom., cov: 34)

Exomes 𝑓: 0.59 ( 242308 hom. )

Consequence

KLHL33
NM_001365790.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.877

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.5052747E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KLHL33	NM_001365790.2 linkuse as main transcript	c.2338G>A	p.Ala780Thr	missense_variant	5/5	ENST00000636854.3	NP_001352719.1
KLHL33	NM_001109997.3 linkuse as main transcript	c.1546G>A	p.Ala516Thr	missense_variant	4/4		NP_001103467.2
KLHL33	XM_011536450.3 linkuse as main transcript	c.2338G>A	p.Ala780Thr	missense_variant	5/5		XP_011534752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KLHL33	ENST00000636854.3 linkuse as main transcript	c.2338G>A	p.Ala780Thr	missense_variant	5/5	5	NM_001365790.2	ENSP00000490040	P1
KLHL33	ENST00000344581.4 linkuse as main transcript	c.1546G>A	p.Ala516Thr	missense_variant	4/4	5		ENSP00000341549
KLHL33	ENST00000637228.1 linkuse as main transcript	c.*497G>A		3_prime_UTR_variant	4/4	5		ENSP00000489731

Frequencies

GnomAD3 genomes

AF:

0.622

AC:

94485

AN:

152020

Hom.:

29715

Cov.:

show subpopulations

Gnomad AFR

AF:

0.721

Gnomad AMI

AF:

0.644

Gnomad AMR

AF:

0.553

Gnomad ASJ

AF:

0.579

Gnomad EAS

AF:

0.602

Gnomad SAS

AF:

0.686

Gnomad FIN

AF:

0.617

Gnomad MID

AF:

0.666

Gnomad NFE

AF:

0.575

Gnomad OTH

AF:

0.644

GnomAD3 exomes

AF:

0.591

AC:

92430

AN:

156406

Hom.:

27731

AF XY:

0.599

AC XY:

49661

AN XY:

82894

show subpopulations

Gnomad AFR exome

AF:

0.721

Gnomad AMR exome

AF:

0.479

Gnomad ASJ exome

AF:

0.591

Gnomad EAS exome

AF:

0.589

Gnomad SAS exome

AF:

0.674

Gnomad FIN exome

AF:

0.617

Gnomad NFE exome

AF:

0.581

Gnomad OTH exome

AF:

0.600

GnomAD4 exome

AF:

0.587

AC:

821111

AN:

1399298

Hom.:

242308

Cov.:

AF XY:

0.589

AC XY:

406780

AN XY:

690162

show subpopulations

Gnomad4 AFR exome

AF:

0.724

Gnomad4 AMR exome

AF:

0.493

Gnomad4 ASJ exome

AF:

0.597

Gnomad4 EAS exome

AF:

0.585

Gnomad4 SAS exome

AF:

0.672

Gnomad4 FIN exome

AF:

0.607

Gnomad4 NFE exome

AF:

0.577

Gnomad4 OTH exome

AF:

0.604

GnomAD4 genome

AF:

0.622

AC:

94597

AN:

152138

Hom.:

29766

Cov.:

AF XY:

0.626

AC XY:

46523

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.722

Gnomad4 AMR

AF:

0.554

Gnomad4 ASJ

AF:

0.579

Gnomad4 EAS

AF:

0.601

Gnomad4 SAS

AF:

0.686

Gnomad4 FIN

AF:

0.617

Gnomad4 NFE

AF:

0.575

Gnomad4 OTH

AF:

0.645

Alfa

AF:

0.579

Hom.:

36213

Bravo

AF:

0.619

TwinsUK

AF:

0.593

AC:

2197

ALSPAC

AF:

0.581

AC:

2241

ESP6500AA

AF:

0.715

AC:

989

ESP6500EA

AF:

0.577

AC:

1835

ExAC

AF:

0.608

AC:

14960

Asia WGS

AF:

0.624

AC:

2173

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.55

DANN

Benign

0.29

DEOGEN2

Benign

0.0024

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.12

T;T

MetaRNN

Benign

0.0000015

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

.;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

0.22

.;N

REVEL

Benign

0.055

Sift

Benign

1.0

.;T

Sift4G

Benign

0.98

.;T

Polyphen

0.0010

.;B

Vest4

0.018

ClinPred

0.00059

GERP RS

-1.8

Varity_R

0.032

gMVP

0.27

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