Variant 16-84657589-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_024731.4(KLHL36):c.782C>T(p.Ala261Val) variant causes a missense change. The variant allele was found at a frequency of 0.000497 in 1,611,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00050 ( 0 hom. )

Consequence

KLHL36
NM_024731.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.47

Variant links:

Genes affected

KLHL36 (HGNC:17844): (kelch like family member 36) Enables cullin family protein binding activity. Predicted to be involved in protein ubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

KLHL36 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=0.073245615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL36	NM_024731.4 linkuse as main transcript	c.782C>T	p.Ala261Val	missense_variant	3/5	ENST00000564996.6	NP_079007.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL36	ENST00000564996.6 linkuse as main transcript	c.782C>T	p.Ala261Val	missense_variant	3/5	1	NM_024731.4	ENSP00000456743	P1	Q8N4N3-1
KLHL36	ENST00000258157.9 linkuse as main transcript	c.782C>T	p.Ala261Val	missense_variant	3/4	1		ENSP00000258157		Q8N4N3-2

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000583

AC:

143

AN:

245124

Hom.:

AF XY:

0.000635

AC XY:

AN XY:

133802

show subpopulations

Gnomad AFR exome

AF:

0.000128

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.000151

Gnomad NFE exome

AF:

0.00116

Gnomad OTH exome

AF:

0.000826

GnomAD4 exome

AF:

0.000502

AC:

732

AN:

1458732

Hom.:

Cov.:

AF XY:

0.000536

AC XY:

389

AN XY:

725862

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.000158

Gnomad4 NFE exome

AF:

0.000608

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.000453

AC:

AN:

152378

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000957

Hom.:

Bravo

AF:

0.000404

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000931

AC:

ExAC

AF:

0.000677

AC:

EpiCase

AF:

0.00147

EpiControl

AF:

0.00113

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 06, 2022

The c.782C>T (p.A261V) alteration is located in exon 3 (coding exon 2) of the KLHL36 gene. This alteration results from a C to T substitution at nucleotide position 782, causing the alanine (A) at amino acid position 261 to be replaced by a valine (V). 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

0.14

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.027

T;.

Eigen

Benign

0.084

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.073

T;T

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.43

N;N

REVEL

Benign

0.21

Sift

Benign

0.21

T;T

Sift4G

Uncertain

0.015

D;D

Polyphen

0.046

B;B

Vest4

0.58

MVP

0.37

MPC

0.57

ClinPred

0.023

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.092

gMVP

0.48

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