Variant 14-44934476-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017658.5(KLHL28):c.982G>A(p.Val328Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000573 in 1,613,858 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 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 0 hom. )

Consequence

KLHL28
NM_017658.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.57

Variant links:

Genes affected

KLHL28 (HGNC:19741): (kelch like family member 28)

KLHL28 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19898126).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL28	NM_017658.5 linkuse as main transcript	c.982G>A	p.Val328Ile	missense_variant	3/5	ENST00000396128.9	NP_060128.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL28	ENST00000396128.9 linkuse as main transcript	c.982G>A	p.Val328Ile	missense_variant	3/5	1	NM_017658.5	ENSP00000379434	P1	Q9NXS3-1
KLHL28	ENST00000355081.3 linkuse as main transcript	c.1024G>A	p.Val342Ile	missense_variant	3/5	1		ENSP00000347193

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

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:

0.000529

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000339

AC:

AN:

251062

Hom.:

AF XY:

0.000346

AC XY:

AN XY:

135694

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000669

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000605

AC:

884

AN:

1461638

Hom.:

Cov.:

AF XY:

0.000545

AC XY:

396

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000734

Gnomad4 OTH exome

AF:

0.000712

GnomAD4 genome

AF:

0.000263

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0000963

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:

0.000529

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000563

Hom.:

Bravo

AF:

0.000295

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000379

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2023

The c.982G>A (p.V328I) alteration is located in exon 3 (coding exon 2) of the KLHL28 gene. This alteration results from a G to A substitution at nucleotide position 982, causing the valine (V) at amino acid position 328 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.20

T;T

MetaSVM

Uncertain

0.13

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.68

N;N

REVEL

Uncertain

0.50

Sift

Uncertain

0.0060

D;D

Sift4G

Benign

0.37

T;T

Polyphen

0.75

P;.

Vest4

0.28

MVP

0.63

MPC

0.50

ClinPred

0.079

GERP RS

5.4

Varity_R

0.35

gMVP

0.41

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