rs539379766

Variant names:

• chr10-3781535-C-T
• rs539379766
• ENST00000469435.1:c.782G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP2 BP4_Strong BS2

The ENST00000469435.1(KLF6):​c.782G>A​(p.Arg261Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,560,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.00073 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000078 (0 hom.)
• Consequence: KLF6 ENST00000469435.1 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.528
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -7 ACMG points.

• 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: 1.628 (below the threshold of 3.09).
• BP4: Computational evidence support a benign effect (MetaRNN=0.003863871).
• BS2: High AC in GnomAd4 at 112 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000469435.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF6	NM_001300.6	MANE Select	c.676+106G>A		intron	N/A	NP_001291.3
	KLF6	NM_001160124.2		c.550+232G>A		intron	N/A	NP_001153596.1
	KLF6	NM_001160125.2		c.676+106G>A		intron	N/A	NP_001153597.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF6	ENST00000469435.1	TSL:1	c.782G>A	p.Arg261Lys	missense	Exon 2 of 2	ENSP00000419079.1
	KLF6	ENST00000497571.6	TSL:1 MANE Select	c.676+106G>A		intron	N/A	ENSP00000419923.1
	KLF6	ENST00000875520.1		c.676+106G>A		intron	N/A	ENSP00000545579.1

Frequencies

GnomAD3 genomes AF: 0.000736 AC: 112 AN: 152274 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000133 AC: 22 AN: 165522 AF XY: 0.000124

Gnomad AFR exome AF: 0.00205

Gnomad AMR exome AF: 0.000158

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000214

GnomAD4 exome AF: 0.0000781 AC: 110 AN: 1408010 Hom.: 0 Cov.: 32 AF XY: 0.0000719 AC XY: 50 AN XY: 695660

African (AFR) AF: 0.00264 AC: 84 AN: 31874

American (AMR) AF: 0.000138 AC: 5 AN: 36228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25282

East Asian (EAS) AF: 0.00 AC: 0 AN: 36148

South Asian (SAS) AF: 0.00 AC: 0 AN: 80758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49382

Middle Eastern (MID) AF: 0.000351 AC: 2 AN: 5704

European-Non Finnish (NFE) AF: 0.00000461 AC: 5 AN: 1084126

Other (OTH) AF: 0.000239 AC: 14 AN: 58508

GnomAD4 genome AF: 0.000735 AC: 112 AN: 152392 Hom.: 0 Cov.: 33 AF XY: 0.000751 AC XY: 56 AN XY: 74526

African (AFR) AF: 0.00257 AC: 107 AN: 41602

American (AMR) AF: 0.000261 AC: 4 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000511 Hom.: 0

Bravo AF: 0.000910

ExAC AF: 0.000184 AC: 21

ClinVar

ClinVar submissions as Germline

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.7
DANN	Benign	0.93
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.53
PROVEAN	Benign	0.23	N
REVEL	Benign	0.012
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.034	B
Vest4		0.075
MVP		0.21
ClinPred		0.074	T
GERP RS		2.7
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs539379766; hg19: chr10-3823727;