10-3781852-G-C

Variant names:

• chr10-3781852-G-C
• NM_001300.6:c.465C>G

Variant summary

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

The NM_001300.6(KLF6):​c.465C>G​(p.Ser155Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. 13/21 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: 6.8e-7 (0 hom.)
• Consequence: KLF6 NM_001300.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16149423).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF6	NM_001300.6	c.465C>G	p.Ser155Arg	missense_variant	Exon 2 of 4	ENST00000497571.6	NP_001291.3
KLF6	NM_001160124.2	c.465C>G	p.Ser155Arg	missense_variant	Exon 2 of 4		NP_001153596.1
KLF6	NM_001160125.2	c.465C>G	p.Ser155Arg	missense_variant	Exon 2 of 3		NP_001153597.1
KLF6	NR_027653.2	n.660C>G		non_coding_transcript_exon_variant	Exon 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF6	ENST00000497571.6	c.465C>G	p.Ser155Arg	missense_variant	Exon 2 of 4	1	NM_001300.6	ENSP00000419923.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T;.;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.066
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.77	T;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.5	M;M;M
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.031
Sift	Benign	0.038	D;D;D
Sift4G	Benign	0.32	T;T;T
Polyphen		0.11	B;.;P
Vest4		0.17
MutPred		0.27		Loss of phosphorylation at S155 (P = 0.0037);Loss of phosphorylation at S155 (P = 0.0037);Loss of phosphorylation at S155 (P = 0.0037);
MVP		0.43
MPC		1.1
ClinPred		0.73	D
GERP RS		2.3
Varity_R		0.14
gMVP		0.46

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: chr10-3824044;