chr10-3782078-T-C

Position:

• chr10-3782078-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001300.6(KLF6):​c.239A>G​(p.Lys80Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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: 0.0000027 (0 hom.)
• Consequence: KLF6 NM_001300.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.99

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]

KLF6 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22510776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF6	NM_001300.6	c.239A>G	p.Lys80Arg	missense_variant	2/4	ENST00000497571.6	NP_001291.3
KLF6	NM_001160124.2	c.239A>G	p.Lys80Arg	missense_variant	2/4		NP_001153596.1
KLF6	NM_001160125.2	c.239A>G	p.Lys80Arg	missense_variant	2/3		NP_001153597.1
KLF6	NR_027653.2	n.434A>G		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF6	ENST00000497571.6	c.239A>G	p.Lys80Arg	missense_variant	2/4	1	NM_001300.6	ENSP00000419923.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 25, 2024

The c.239A>G (p.K80R) alteration is located in exon 2 (coding exon 2) of the KLF6 gene. This alteration results from a A to G substitution at nucleotide position 239, causing the lysine (K) at amino acid position 80 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T;.;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.85	D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.6	M;M;M
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.98	N;N;N
REVEL	Benign	0.086
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.52	T;T;T
Polyphen		0.12	B;.;P
Vest4		0.37
MutPred		0.33		Loss of ubiquitination at K80 (P = 0.0012);Loss of ubiquitination at K80 (P = 0.0012);Loss of ubiquitination at K80 (P = 0.0012);
MVP		0.82
MPC		1.7
ClinPred		0.85	D
GERP RS		3.7
Varity_R		0.099
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-3824270;