Variant 1-6599377-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014851.4(KLHL21):c.1097C>T(p.Ala366Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000855 in 1,613,610 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00048 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

KLHL21
NM_014851.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 10.0

Variant links:

Genes affected

KLHL21 (HGNC:29041): (kelch like family member 21) Enables cullin family protein binding activity. Contributes to ubiquitin-protein transferase activity. Involved in chromosome passenger complex localization to spindle midzone; protein ubiquitination; and regulation of cytokinesis. Located in polar microtubule. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

KLHL21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06425783).

BP6

Variant 1-6599377-G-A is Benign according to our data. Variant chr1-6599377-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3056491.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLHL21	NM_014851.4 linkuse as main transcript	c.1097C>T	p.Ala366Val	missense_variant	2/4	ENST00000377658.8
KLHL21	NM_001324309.2 linkuse as main transcript	c.1097C>T	p.Ala366Val	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLHL21	ENST00000377658.8 linkuse as main transcript	c.1097C>T	p.Ala366Val	missense_variant	2/4	1	NM_014851.4	P1	Q9UJP4-1

Frequencies

GnomAD3 genomes

AF:

0.000480

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000130

AC:

AN:

247014

Hom.:

AF XY:

0.000119

AC XY:

AN XY:

134020

show subpopulations

Gnomad AFR exome

AF:

0.00200

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000445

AC:

AN:

1461352

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

726954

show subpopulations

Gnomad4 AFR exome

AF:

0.00176

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000479

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00176

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000139

Hom.:

Bravo

AF:

0.000635

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000181

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

KLHL21-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 28, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Uncertain

0.55

D;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.064

T;T

MetaSVM

Uncertain

0.066

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.1

D;D

REVEL

Uncertain

0.47

Sift

Uncertain

0.015

D;D

Sift4G

Benign

0.096

T;D

Polyphen

0.85

P;P

Vest4

0.59

MVP

0.93

MPC

0.40

ClinPred

0.16

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.41

gMVP

0.35

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