Genetic Variant KLF6:p.Ser142Cys (chr10-3781892-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001300.6(KLF6):c.425C>G(p.Ser142Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,204 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. 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:

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 1 ACMG points.

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=0.2136155).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KLF6	NM_001300.6	MANE Select	c.425C>G	p.Ser142Cys	missense	Exon 2 of 4	NP_001291.3
KLF6	NM_001160124.2		c.425C>G	p.Ser142Cys	missense	Exon 2 of 4	NP_001153596.1	D3GC14
KLF6	NM_001160125.2		c.425C>G	p.Ser142Cys	missense	Exon 2 of 3	NP_001153597.1	Q99612-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KLF6	ENST00000497571.6	TSL:1 MANE Select	c.425C>G	p.Ser142Cys	missense	Exon 2 of 4	ENSP00000419923.1	Q99612-1
KLF6	ENST00000469435.1	TSL:1	c.425C>G	p.Ser142Cys	missense	Exon 2 of 2	ENSP00000419079.1	Q99612-2
KLF6	ENST00000875520.1		c.425C>G	p.Ser142Cys	missense	Exon 2 of 4	ENSP00000545579.1

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:

0.00

Gnomad SAS

AF:

0.000207

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:

152204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Uncertain

0.61

Eigen

Benign

0.014

Eigen_PC

Benign

0.060

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.77

M_CAP

Benign

0.021

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.2

PhyloP100

5.6

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.3

REVEL

Benign

0.076

Sift

Benign

0.083

Sift4G

Benign

0.070

Polyphen

0.035

Vest4

0.21

MutPred

0.33

Gain of helix (P = 0.0143)

MVP

0.52

MPC

0.81

ClinPred

0.40

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.095

gMVP

0.36

Mutation Taster

=56/44

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over