Variant chr2-169735174-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000392647.7(KLHL23):c.160G>A(p.Val54Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,612,274 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

KLHL23
ENST00000392647.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.76

Variant links:

Genes affected

KLHL23 (HGNC:27506): (kelch like family member 23)

KLHL23 links:

PHOSPHO2-KLHL23 (HGNC:):

PHOSPHO2-KLHL23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL23	NM_144711.6 linkuse as main transcript	c.160G>A	p.Val54Ile	missense_variant	2/4	ENST00000392647.7	NP_653312.2	Q8NBE8
PHOSPHO2-KLHL23	NM_001199290.3 linkuse as main transcript	c.160G>A	p.Val54Ile	missense_variant	4/6		NP_001186219.1	Q8NBE8
PHOSPHO2-KLHL23	NR_144936.2 linkuse as main transcript	n.359-6211G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KLHL23	ENST00000392647.7 linkuse as main transcript	c.160G>A	p.Val54Ile	missense_variant	2/4	1	NM_144711.6	ENSP00000376419.2	Q8NBE8
KLHL23	ENST00000272797.8 linkuse as main transcript	c.160G>A	p.Val54Ile	missense_variant	4/6	2		ENSP00000272797.4	Q8NBE8
KLHL23	ENST00000602521.1 linkuse as main transcript	c.-266-6211G>A		intron_variant		3		ENSP00000475081.1	S4R452
KLHL23	ENST00000498202.6 linkuse as main transcript	c.-266-6211G>A		intron_variant		3		ENSP00000474581.1	S4R3P4

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

248812

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134494

show subpopulations

Gnomad AFR exome

AF:

0.0000628

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000295

AC:

AN:

1459974

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

726116

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000342

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

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

Dec 27, 2023

The c.160G>A (p.V54I) alteration is located in exon 2 (coding exon 1) of the KLHL23 gene. This alteration results from a G to A substitution at nucleotide position 160, causing the valine (V) at amino acid position 54 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

0.11

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;T

Eigen

Uncertain

0.60

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.88

.;D

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.2

L;L

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.72

N;N

REVEL

Benign

0.27

Sift

Uncertain

0.019

D;D

Sift4G

Benign

0.18

T;T

Polyphen

0.94

P;P

Vest4

0.34

MVP

0.80

MPC

0.088

ClinPred

0.15

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.40

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