Variant 2-169735232-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_144711.6(KLHL23):c.218A>C(p.Lys73Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KLHL23
NM_144711.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.52

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30710667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL23	NM_144711.6 linkuse as main transcript	c.218A>C	p.Lys73Thr	missense_variant	2/4	ENST00000392647.7	NP_653312.2	Q8NBE8
PHOSPHO2-KLHL23	NM_001199290.3 linkuse as main transcript	c.218A>C	p.Lys73Thr	missense_variant	4/6		NP_001186219.1	Q8NBE8
PHOSPHO2-KLHL23	NR_144936.2 linkuse as main transcript	n.359-6153A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KLHL23	ENST00000392647.7 linkuse as main transcript	c.218A>C	p.Lys73Thr	missense_variant	2/4	1	NM_144711.6	ENSP00000376419.2	Q8NBE8
KLHL23	ENST00000272797.8 linkuse as main transcript	c.218A>C	p.Lys73Thr	missense_variant	4/6	2		ENSP00000272797.4	Q8NBE8
KLHL23	ENST00000602521.1 linkuse as main transcript	c.-266-6153A>C		intron_variant		3		ENSP00000475081.1	S4R452
KLHL23	ENST00000498202.6 linkuse as main transcript	c.-266-6153A>C		intron_variant		3		ENSP00000474581.1	S4R3P4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000418

AC:

AN:

239008

Hom.:

AF XY:

0.00000772

AC XY:

AN XY:

129616

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000909

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450808

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

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

Sep 03, 2024

The c.218A>C (p.K73T) alteration is located in exon 2 (coding exon 1) of the KLHL23 gene. This alteration results from a A to C substitution at nucleotide position 218, causing the lysine (K) at amino acid position 73 to be replaced by a threonine (T). 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

Uncertain

0.41

BayesDel_addAF

Benign

-0.0082

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

.;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.31

T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.3

L;L

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.54

N;N

REVEL

Benign

0.25

Sift

Benign

0.11

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.025

B;B

Vest4

0.37

MutPred

0.50

Loss of solvent accessibility (P = 0.0249);Loss of solvent accessibility (P = 0.0249);

MVP

0.78

MPC

0.40

ClinPred

0.38

GERP RS

5.8

Varity_R

0.22

gMVP

0.53

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