Variant chr2-23562263-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_052920.2(KLHL29):c.67G>A(p.Val23Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,550,072 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000097 ( 1 hom. )

Consequence

KLHL29
NM_052920.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.68

Variant links:

Genes affected

KLHL29 (HGNC:29404): (kelch like family member 29)

KLHL29 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0092512965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL29	NM_052920.2 linkuse as main transcript	c.67G>A	p.Val23Ile	missense_variant	3/14	ENST00000486442.6	NP_443152.1
KLHL29	XM_006711929.4 linkuse as main transcript	c.67G>A	p.Val23Ile	missense_variant	2/13		XP_006711992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL29	ENST00000486442.6 linkuse as main transcript	c.67G>A	p.Val23Ile	missense_variant	3/14	5	NM_052920.2	ENSP00000420659	P1	Q96CT2-1
KLHL29	ENST00000489446.1 linkuse as main transcript	n.148G>A		non_coding_transcript_exon_variant	2/4	1

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000580

AC:

AN:

149906

Hom.:

AF XY:

0.000437

AC XY:

AN XY:

80124

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.00261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00167

Gnomad SAS exome

AF:

0.0000442

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000700

GnomAD4 exome

AF:

0.0000966

AC:

135

AN:

1397754

Hom.:

Cov.:

AF XY:

0.0000841

AC XY:

AN XY:

689384

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.00239

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000812

Gnomad4 SAS exome

AF:

0.0000758

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000834

Gnomad4 OTH exome

AF:

0.0000863

GnomAD4 genome

AF:

0.000249

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.000450

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000390

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

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

Oct 04, 2022

The c.67G>A (p.V23I) alteration is located in exon 3 (coding exon 1) of the KLHL29 gene. This alteration results from a G to A substitution at nucleotide position 67, causing the valine (V) at amino acid position 23 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

0.072

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

Eigen

Benign

-0.093

Eigen_PC

Benign

0.056

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.78

M_CAP

Benign

0.033

MetaRNN

Benign

0.0093

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.13

REVEL

Benign

0.12

Sift

Benign

0.10

Sift4G

Benign

0.14

Vest4

0.051

MVP

0.38

ClinPred

0.017

GERP RS

3.8

Varity_R

0.025

gMVP

0.051

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