rs121909139

Variant names:

• chr10-3781971-A-G
• rs121909139
• NM_001300.6:c.346T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2 PP2 PP5 BP4

The NM_001300.6(KLF6):​c.346T>C​(p.Ser116Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KLF6 NM_001300.6 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.91
• Publications: 1 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: Uncertain_significance. The variant received 3 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).
• PP5: Variant 10-3781971-A-G is Pathogenic according to our data. Variant chr10-3781971-A-G is described in ClinVar as Pathogenic. ClinVar VariationId is 7569.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.3484761). . Strength limited to SUPPORTING due to the PP5.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF6	NM_001300.6	MANE Select	c.346T>C	p.Ser116Pro	missense	Exon 2 of 4	NP_001291.3
	KLF6	NM_001160124.2		c.346T>C	p.Ser116Pro	missense	Exon 2 of 4	NP_001153596.1
	KLF6	NM_001160125.2		c.346T>C	p.Ser116Pro	missense	Exon 2 of 3	NP_001153597.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF6	ENST00000497571.6	TSL:1 MANE Select	c.346T>C	p.Ser116Pro	missense	Exon 2 of 4	ENSP00000419923.1
	KLF6	ENST00000469435.1	TSL:1	c.346T>C	p.Ser116Pro	missense	Exon 2 of 2	ENSP00000419079.1
	KLF6	ENST00000542957.1	TSL:5	c.346T>C	p.Ser116Pro	missense	Exon 2 of 3	ENSP00000445301.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer, somatic Pathogenic:1

Dec 21, 2001

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.9
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.080
Sift	Benign	0.077	T
Sift4G	Benign	0.10	T
Polyphen		0.81	P
Vest4		0.46
MutPred		0.23		Loss of phosphorylation at S116 (P = 0.0016)
MVP		0.63
MPC		2.1
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.55
gMVP		0.31
Mutation Taster		=0/100	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: rs121909139; hg19: chr10-3824163;