rs121909140

Variant names:

• chr10-3781907-G-T
• rs121909140
• NM_001300.6:c.410C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-3781907-G-T
• chr10-3781907-G-A
• chr10-3781907-G-C

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001300.6(KLF6):​c.410C>A​(p.Ser137*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KLF6 NM_001300.6 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.57
• Publications: 3 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: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 10-3781907-G-T is Pathogenic according to our data. Variant chr10-3781907-G-T is described in ClinVar as Pathogenic. ClinVar VariationId is 7570.Status of the report is no_assertion_criteria_provided, 0 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF6	NM_001300.6	MANE Select	c.410C>A	p.Ser137*	stop_gained	Exon 2 of 4	NP_001291.3
	KLF6	NM_001160124.2		c.410C>A	p.Ser137*	stop_gained	Exon 2 of 4	NP_001153596.1	D3GC14
	KLF6	NM_001160125.2		c.410C>A	p.Ser137*	stop_gained	Exon 2 of 3	NP_001153597.1	Q99612-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF6	ENST00000497571.6	TSL:1 MANE Select	c.410C>A	p.Ser137*	stop_gained	Exon 2 of 4	ENSP00000419923.1	Q99612-1
	KLF6	ENST00000469435.1	TSL:1	c.410C>A	p.Ser137*	stop_gained	Exon 2 of 2	ENSP00000419079.1	Q99612-2
	KLF6	ENST00000875520.1		c.410C>A	p.Ser137*	stop_gained	Exon 2 of 4	ENSP00000545579.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Prostate cancer, somatic (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.48
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Benign	0.48	N
PhyloP100		5.6
Vest4		0.74
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=7/193	disease causing (ClinVar)

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: rs121909140; hg19: chr10-3824099;