chr8-102649114-G-A

Variant names:

• chr8-102649114-G-A
• rs6935
• NM_005655.4:c.*1018C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_005655.4(KLF10):​c.*1018C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000404 in 148,636 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: 𝑓 0.000040 (0 hom., cov: 32)
• Consequence: KLF10 NM_005655.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 9 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS2: High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF10	NM_005655.4	c.*1018C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000285407.11	NP_005646.1
KLF10	NR_103759.2	n.1786C>T		non_coding_transcript_exon_variant	Exon 3 of 3
KLF10	NR_103760.2	n.1909C>T		non_coding_transcript_exon_variant	Exon 4 of 4
KLF10	NM_001032282.4	c.*1018C>T		3_prime_UTR_variant	Exon 4 of 4		NP_001027453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF10	ENST00000285407.11	c.*1018C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_005655.4	ENSP00000285407.6
KLF10	ENST00000395884.3	c.*1018C>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000379222.3
ENSG00000283959	ENST00000731667.1	n.164-17089G>A		intron_variant	Intron 1 of 7
ENSG00000283959	ENST00000731685.1	n.230-17089G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0000404 AC: 6 AN: 148636 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000737

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000404 AC: 6 AN: 148636 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1 AN XY: 72598

African (AFR) AF: 0.00 AC: 0 AN: 38376

American (AMR) AF: 0.0000657 AC: 1 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000737 AC: 5 AN: 67834

Other (OTH) AF: 0.00 AC: 0 AN: 2060

Alfa AF: 0.00 Hom.: 1310

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		0.042
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

dbSNP: rs6935; hg19: chr8-103661342;