NM_001300.6:c.533G>T

Variant names:

• chr10-3781784-C-A
• rs754239177
• NM_001300.6:c.533G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001300.6(KLF6):​c.533G>T​(p.Gly178Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 6.8e-7 (0 hom.)
• Consequence: KLF6 NM_001300.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.82

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35433313).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF6	NM_001300.6	c.533G>T	p.Gly178Val	missense_variant	Exon 2 of 4	ENST00000497571.6	NP_001291.3
KLF6	NM_001160124.2	c.533G>T	p.Gly178Val	missense_variant	Exon 2 of 4		NP_001153596.1
KLF6	NM_001160125.2	c.533G>T	p.Gly178Val	missense_variant	Exon 2 of 3		NP_001153597.1
KLF6	NR_027653.2	n.717+11G>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF6	ENST00000497571.6	c.533G>T	p.Gly178Val	missense_variant	Exon 2 of 4	1	NM_001300.6	ENSP00000419923.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251418 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135908

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T;.;.
Eigen	Benign	0.030
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.85	T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L;L;L
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.078	T;T;T
Sift4G	Benign	0.085	T;T;T
Polyphen		0.034	B;.;P
Vest4		0.61
MutPred		0.30		Loss of catalytic residue at G178 (P = 0.043);Loss of catalytic residue at G178 (P = 0.043);Loss of catalytic residue at G178 (P = 0.043);
MVP		0.65
MPC		2.2
ClinPred		0.50	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.64

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: rs754239177; hg19: chr10-3823976;