Variant 10-3781613-G-A 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.704C>T(p.Ala235Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000385 in 1,609,158 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 2 hom. )

Consequence

KLF6
ENST00000469435.1 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -0.0460

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:

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=0.00426051).

BS2

High AC in GnomAd at 286 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
KLF6	NM_001300.6 linkuse as main transcript	c.676+28C>T	intron_variant	ENST00000497571.6
KLF6	NM_001160124.2 linkuse as main transcript	c.550+154C>T	intron_variant
KLF6	NM_001160125.2 linkuse as main transcript	c.676+28C>T	intron_variant
KLF6	NR_027653.2 linkuse as main transcript	n.717+182C>T	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF6	ENST00000469435.1 linkuse as main transcript	c.704C>T	p.Ala235Val	missense_variant	2/2	1			Q99612-2
KLF6	ENST00000497571.6 linkuse as main transcript	c.676+28C>T		intron_variant		1	NM_001300.6	P1	Q99612-1
KLF6	ENST00000542957.1 linkuse as main transcript	c.676+28C>T		intron_variant		5			Q99612-3
KLF6	ENST00000173785.4 linkuse as main transcript	n.257+182C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00188

AC:

286

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00647

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

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:

0.0000882

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000521

AC:

122

AN:

234248

Hom.:

AF XY:

0.000466

AC XY:

AN XY:

128804

show subpopulations

Gnomad AFR exome

AF:

0.00736

Gnomad AMR exome

AF:

0.000239

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000100

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000876

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000227

AC:

331

AN:

1456828

Hom.:

Cov.:

AF XY:

0.000221

AC XY:

160

AN XY:

724446

show subpopulations

Gnomad4 AFR exome

AF:

0.00608

Gnomad4 AMR exome

AF:

0.000250

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000699

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000883

Gnomad4 OTH exome

AF:

0.000216

GnomAD4 genome

AF:

0.00189

AC:

288

AN:

152330

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

133

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00650

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000594

Hom.:

Bravo

AF:

0.00202

ESP6500AA

AF:

0.00554

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000630

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

-0.63

BayesDel_noAF

Benign

-0.68

Cadd

Benign

7.2

Dann

Uncertain

1.0

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.32

MetaRNN

Benign

0.0043

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

-0.80

REVEL

Benign

0.028

Sift

Benign

0.077

Sift4G

Pathogenic

0.0

Polyphen

0.16

Vest4

0.19

MVP

0.60

ClinPred

0.014

GERP RS

-1.9

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.3

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