Genetic Variant NM_005655.4:c.*1018C>A (chr8-102649114-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005655.4(KLF10):c.*1018C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 149,092 control chromosomes in the GnomAD database, including 15,302 homozygotes. 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 0.45 ( 15260 hom., cov: 32)

Exomes 𝑓: 0.42 ( 42 hom. )

Consequence

KLF10
NM_005655.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0420

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

hypertrophic cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

KLF10 links:

ENSG00000283959 (HGNC:):

ENSG00000283959 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KLF10	NM_005655.4	MANE Select	c.*1018C>A	3_prime_UTR	Exon 4 of 4	NP_005646.1
KLF10	NR_103759.2		n.1786C>A	non_coding_transcript_exon	Exon 3 of 3
KLF10	NR_103760.2		n.1909C>A	non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KLF10	ENST00000285407.11	TSL:1 MANE Select	c.*1018C>A	3_prime_UTR	Exon 4 of 4	ENSP00000285407.6
KLF10	ENST00000395884.3	TSL:1	c.*1018C>A	3_prime_UTR	Exon 4 of 4	ENSP00000379222.3
ENSG00000283959	ENST00000731667.1		n.164-17089G>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.452

AC:

67194

AN:

148560

Hom.:

15249

Cov.:

show subpopulations

Gnomad AFR

AF:

0.375

Gnomad AMI

AF:

0.508

Gnomad AMR

AF:

0.493

Gnomad ASJ

AF:

0.487

Gnomad EAS

AF:

0.583

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.407

Gnomad MID

AF:

0.510

Gnomad NFE

AF:

0.481

Gnomad OTH

AF:

0.452

GnomAD4 exome

AF:

0.419

AC:

180

AN:

430

Hom.:

Cov.:

AF XY:

0.438

AC XY:

113

AN XY:

258

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.422

AC:

179

AN:

424

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.452

AC:

67235

AN:

148662

Hom.:

15260

Cov.:

AF XY:

0.453

AC XY:

32910

AN XY:

72670

show subpopulations

African (AFR)

AF:

0.375

AC:

14431

AN:

38456

American (AMR)

AF:

0.493

AC:

7499

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.487

AC:

1684

AN:

3456

East Asian (EAS)

AF:

0.582

AC:

3009

AN:

5174

South Asian (SAS)

AF:

0.457

AC:

2179

AN:

4772

European-Finnish (FIN)

AF:

0.407

AC:

4270

AN:

10500

Middle Eastern (MID)

AF:

0.517

AC:

151

AN:

292

European-Non Finnish (NFE)

AF:

0.481

AC:

32613

AN:

67806

Other (OTH)

AF:

0.451

AC:

939

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1918

3836

5753

7671

9589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.359

Hom.:

1310

Bravo

AF:

0.448

Asia WGS

AF:

0.503

AC:

1745

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

0.042

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over