Variant 8-102650227-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005655.4(KLF10):c.1348C>T(p.Arg450Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

KLF10
NM_005655.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.92

Variant links:

Genes affected

KLF10 (HGNC:11810): (KLF transcription factor 10) This gene encodes a member of a family of proteins that feature C2H2-type zinc finger domains. The encoded protein is a transcriptional repressor that acts as an effector of transforming growth factor beta signaling. Activity of this protein may inhibit the growth of cancers, particularly pancreatic cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

KLF10 links:

KLF10 (HGNC:):

KLF10 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF10	NM_005655.4 linkuse as main transcript	c.1348C>T	p.Arg450Cys	missense_variant	4/4	ENST00000285407.11	NP_005646.1	Q13118-1
KLF10	NM_001032282.4 linkuse as main transcript	c.1315C>T	p.Arg439Cys	missense_variant	4/4		NP_001027453.1	Q13118-2
KLF10	NR_103759.2 linkuse as main transcript	n.673C>T		non_coding_transcript_exon_variant	3/3
KLF10	NR_103760.2 linkuse as main transcript	n.796C>T		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF10	ENST00000285407.11 linkuse as main transcript	c.1348C>T	p.Arg450Cys	missense_variant	4/4	1	NM_005655.4	ENSP00000285407.6		Q13118-1
KLF10	ENST00000395884.3 linkuse as main transcript	c.1315C>T	p.Arg439Cys	missense_variant	4/4	1		ENSP00000379222.3		Q13118-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251480

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135912

show subpopulations

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727248

show subpopulations

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2024

The c.1348C>T (p.R450C) alteration is located in exon 4 (coding exon 4) of the KLF10 gene. This alteration results from a C to T substitution at nucleotide position 1348, causing the arginine (R) at amino acid position 450 to be replaced by a cysteine (C). 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

Pathogenic

0.98

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

D;.

Eigen

Uncertain

0.59

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

D;D

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.55

D;D

MetaSVM

Benign

-0.33

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-6.9

D;D

REVEL

Uncertain

0.40

Sift

Benign

0.041

D;D

Sift4G

Uncertain

0.037

D;D

Polyphen

0.69

P;.

Vest4

0.45

MutPred

0.47

Loss of phosphorylation at S453 (P = 0.0497);.;

MVP

0.88

MPC

2.3

ClinPred

0.88

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.41

gMVP

0.91

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over