8-102650146-C-T

Variant names:

• chr8-102650146-C-T
• NM_005655.4:c.1429G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005655.4(KLF10):​c.1429G>A​(p.Ala477Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KLF10 NM_005655.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.19
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000283959 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059284717).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005655.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF10	NM_005655.4	MANE Select	c.1429G>A	p.Ala477Thr	missense	Exon 4 of 4	NP_005646.1	Q13118-1
	KLF10	NM_001032282.4		c.1396G>A	p.Ala466Thr	missense	Exon 4 of 4	NP_001027453.1	Q13118-2
	KLF10	NR_103759.2		n.754G>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF10	ENST00000285407.11	TSL:1 MANE Select	c.1429G>A	p.Ala477Thr	missense	Exon 4 of 4	ENSP00000285407.6	Q13118-1
	KLF10	ENST00000395884.3	TSL:1	c.1396G>A	p.Ala466Thr	missense	Exon 4 of 4	ENSP00000379222.3	Q13118-2
	KLF10	ENST00000907828.1		c.1426G>A	p.Ala476Thr	missense	Exon 4 of 4	ENSP00000577887.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.11	N
PhyloP100		1.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.059
Sift	Benign	0.29	T
Sift4G	Benign	0.40	T
Polyphen		0.0070	B
Vest4		0.097
MutPred		0.13		Gain of glycosylation at A477 (P = 0.0075)
MVP		0.41
MPC		1.2
ClinPred		0.21	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.50
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

hg19: chr8-103662374;