chr10-3782078-T-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 5P and 2B. PM1PM2PP2BP4_Moderate

The NM_001300.6(KLF6):c.239A>G(p.Lys80Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

KLF6
NM_001300.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.99

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 3 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 1 benign (83%) in NM_001300.6

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 5 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. Gene score misZ: 1.8535 (below the threshold of 3.09). Trascript score misZ: 2.6969 (below the threshold of 3.09).

BP4

Computational evidence support a benign effect (MetaRNN=0.22510776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF6	NM_001300.6 link	c.239A>G	p.Lys80Arg	missense_variant	Exon 2 of 4	ENST00000497571.6	NP_001291.3	Q99612-1
KLF6	NM_001160124.2 link	c.239A>G	p.Lys80Arg	missense_variant	Exon 2 of 4		NP_001153596.1	Q99612D3GC14
KLF6	NM_001160125.2 link	c.239A>G	p.Lys80Arg	missense_variant	Exon 2 of 3		NP_001153597.1	Q99612-3
KLF6	NR_027653.2 link	n.434A>G		non_coding_transcript_exon_variant	Exon 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF6	ENST00000497571.6 link	c.239A>G	p.Lys80Arg	missense_variant	Exon 2 of 4	1	NM_001300.6	ENSP00000419923.1		Q99612-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111994

Other (OTH)

AF:

0.0000331

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 25, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.239A>G (p.K80R) alteration is located in exon 2 (coding exon 2) of the KLF6 gene. This alteration results from a A to G substitution at nucleotide position 239, causing the lysine (K) at amino acid position 80 to be replaced by an arginine (R). 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

0.11

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

T;.;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.85

D;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.6

M;M;M

PhyloP100

4.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.98

N;N;N

REVEL

Benign

0.086

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.52

T;T;T

Polyphen

0.12

B;.;P

Vest4

0.37

MutPred

0.33

Loss of ubiquitination at K80 (P = 0.0012);Loss of ubiquitination at K80 (P = 0.0012);Loss of ubiquitination at K80 (P = 0.0012);

MVP

0.82

MPC

1.7

ClinPred

0.85

GERP RS

3.7

Varity_R

0.099

gMVP

0.45

Mutation Taster

=89/11

polymorphism

(source)

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

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chr10-3782078-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over