Variant rs539379766 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_StrongBS2

The ENST00000469435.1(KLF6):c.782G>A(p.Arg261Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,560,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

KLF6
ENST00000469435.1 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.528

Variant links:

Genes affected

KLF6 (HGNC:2235): (KLF transcription factor 6) This gene encodes a member of the Kruppel-like family of transcription factors. The zinc finger protein is a transcriptional activator, and functions as a tumor suppressor. Multiple transcript variants encoding different isoforms have been found for this gene, some of which are implicated in carcinogenesis. [provided by RefSeq, May 2009]

KLF6 links:

KLF6 (HGNC:):

KLF6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM1

In a chain Krueppel-like factor 6 (size 282) in uniprot entity KLF6_HUMAN there are 5 pathogenic changes around while only 2 benign (71%) in ENST00000469435.1

BP4

Computational evidence support a benign effect (MetaRNN=0.003863871).

BS2

High AC in GnomAd4 at 112 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
KLF6	NM_001300.6 linkuse as main transcript	c.676+106G>A	intron_variant	ENST00000497571.6	NP_001291.3	Q99612-1
KLF6	NM_001160124.2 linkuse as main transcript	c.550+232G>A	intron_variant		NP_001153596.1	Q99612D3GC14
KLF6	NM_001160125.2 linkuse as main transcript	c.676+106G>A	intron_variant		NP_001153597.1	Q99612-3
KLF6	NR_027653.2 linkuse as main transcript	n.717+260G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KLF6	ENST00000469435.1 linkuse as main transcript	c.782G>A	p.Arg261Lys	missense_variant	2/2	1		ENSP00000419079.1	Q99612-2
KLF6	ENST00000497571.6 linkuse as main transcript	c.676+106G>A		intron_variant		1	NM_001300.6	ENSP00000419923.1	Q99612-1
KLF6	ENST00000542957.1 linkuse as main transcript	c.676+106G>A		intron_variant		5		ENSP00000445301.1	Q99612-3
KLF6	ENST00000173785.4 linkuse as main transcript	n.257+260G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000736

AC:

112

AN:

152274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000478

GnomAD3 exomes

AF:

0.000133

AC:

AN:

165522

Hom.:

AF XY:

0.000124

AC XY:

AN XY:

88786

show subpopulations

Gnomad AFR exome

AF:

0.00205

Gnomad AMR exome

AF:

0.000158

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:

0.000214

GnomAD4 exome

AF:

0.0000781

AC:

110

AN:

1408010

Hom.:

Cov.:

AF XY:

0.0000719

AC XY:

AN XY:

695660

show subpopulations

Gnomad4 AFR exome

AF:

0.00264

Gnomad4 AMR exome

AF:

0.000138

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:

0.00000461

Gnomad4 OTH exome

AF:

0.000239

GnomAD4 genome

AF:

0.000735

AC:

112

AN:

152392

Hom.:

Cov.:

AF XY:

0.000751

AC XY:

AN XY:

74526

show subpopulations

Gnomad4 AFR

AF:

0.00257

Gnomad4 AMR

AF:

0.000261

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:

0.000473

Alfa

AF:

0.000480

Hom.:

Bravo

AF:

0.000910

ExAC

AF:

0.000184

AC:

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.7

DANN

Benign

0.93

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.16

M_CAP

Benign

0.0058

MetaRNN

Benign

0.0039

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.23

REVEL

Benign

0.012

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.034

Vest4

0.075

MVP

0.21

ClinPred

0.074

GERP RS

2.7

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