10-3781971-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1 PM2 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

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 4 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
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 10-3781971-A-G is Pathogenic according to our data. Variant chr10-3781971-A-G is described in ClinVar as [Pathogenic]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF6	NM_001300.6	c.346T>C	p.Ser116Pro	missense_variant	2/4	ENST00000497571.6
KLF6	NM_001160124.2	c.346T>C	p.Ser116Pro	missense_variant	2/4
KLF6	NM_001160125.2	c.346T>C	p.Ser116Pro	missense_variant	2/3
KLF6	NR_027653.2	n.541T>C		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF6	ENST00000497571.6	c.346T>C	p.Ser116Pro	missense_variant	2/4	1	NM_001300.6	P1

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

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 21, 2001

- -

Computational scores

Source: dbNSFP v4.3

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;D;D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.5	M;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.7	D;N;N
REVEL	Benign	0.080
Sift	Benign	0.077	T;D;T
Sift4G	Benign	0.10	T;T;T
Polyphen		0.81	P;.;D
Vest4		0.46
MutPred		0.23		Loss of phosphorylation at S116 (P = 0.0016);Loss of phosphorylation at S116 (P = 0.0016);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

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: rs121909139; hg19: chr10-3824163;