dbSNP rs11252089: KLF6:p.Ser142Phe (chr10-3781892-G-A) – ACMG Classification: Uncertain_significance (5 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM1PM2PP2

The NM_001300.6(KLF6):c.425C>T(p.Ser142Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,322 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S142Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

KLF6
NM_001300.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.61

Publications

1 publications found

Variant links:

COSMIC-nc: COSV107181430

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 5 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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF6	NM_001300.6 link	c.425C>T	p.Ser142Phe	missense_variant	Exon 2 of 4	ENST00000497571.6	NP_001291.3	Q99612-1
KLF6	NM_001160124.2 link	c.425C>T	p.Ser142Phe	missense_variant	Exon 2 of 4		NP_001153596.1	Q99612D3GC14
KLF6	NM_001160125.2 link	c.425C>T	p.Ser142Phe	missense_variant	Exon 2 of 3		NP_001153597.1	Q99612-3
KLF6	NR_027653.2 link	n.620C>T		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.425C>T	p.Ser142Phe	missense_variant	Exon 2 of 4	1	NM_001300.6	ENSP00000419923.1		Q99612-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41582

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2112

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

Alfa

AF:

0.0000142

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

0.0022

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.83

D;.;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Benign

0.55

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.047

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-0.39

MutationAssessor

Uncertain

2.6

M;M;M

PhyloP100

5.6

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.013

D;D;D

Sift4G

Uncertain

0.033

D;D;D

Polyphen

0.99

D;.;P

Vest4

0.45

MutPred

0.34

Gain of catalytic residue at S142 (P = 0.0067);Gain of catalytic residue at S142 (P = 0.0067);Gain of catalytic residue at S142 (P = 0.0067);

MVP

0.61

MPC

1.6

ClinPred

0.98

GERP RS

4.1

Varity_R

0.19

gMVP

0.37

Mutation Taster

=57/43

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over