rs121909140

chr10-3781907-G-Achr10-3781907-G-Cchr10-3781907-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM1 BP4

The NM_001300.6(KLF6):c.410C>T(p.Ser137Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: KLF6 NM_001300.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.57

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 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 NM_001300.6
• BP4: Computational evidence support a benign effect (MetaRNN=0.30471784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF6	NM_001300.6	c.410C>T	p.Ser137Leu	missense_variant	2/4	ENST00000497571.6
KLF6	NM_001160124.2	c.410C>T	p.Ser137Leu	missense_variant	2/4
KLF6	NM_001160125.2	c.410C>T	p.Ser137Leu	missense_variant	2/3
KLF6	NR_027653.2	n.605C>T		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF6	ENST00000497571.6	c.410C>T	p.Ser137Leu	missense_variant	2/4	1	NM_001300.6	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251202 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135766

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461882 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000899

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.16
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.61	D;.;.
Eigen	Benign	0.098
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.53	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.5	M;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.26	T;T;T
Sift4G	Benign	0.36	T;T;T
Polyphen		0.47	P;.;P
Vest4		0.49
MutPred		0.30		Loss of glycosylation at S137 (P = 0.0048);Loss of glycosylation at S137 (P = 0.0048);Loss of glycosylation at S137 (P = 0.0048);
MVP		0.80
MPC		0.82
ClinPred		0.31	T
GERP RS		5.0
Varity_R		0.094
gMVP		0.36

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

Other links and lift over

dbSNP: rs121909140; hg19: chr10-3824099; COSMIC: COSV51494331; COSMIC: COSV51494331;