chrX-56265420-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_007250.5(KLF8):c.322A>G(p.Ile108Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00629 in 1,209,391 control chromosomes in the GnomAD database, including 18 homozygotes. There are 2,499 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 1 hom., 136 hem., cov: 22)

Exomes 𝑓: 0.0065 ( 17 hom. 2363 hem. )

Consequence

KLF8
NM_007250.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.354

Publications

5 publications found

Variant links:

Genes affected

KLF8 (HGNC:6351): (KLF transcription factor 8) This gene encodes a protein which is a member of the Sp/KLF family of transcription factors. Members of this family contain a C-terminal DNA-binding domain with three Kruppel-like zinc fingers. The encoded protein is thought to play an important role in the regulation of epithelial to mesenchymal transition, a process which occurs normally during development but also during metastasis. A pseudogene has been identified on chromosome 16. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

KLF8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP6

Variant X-56265420-A-G is Benign according to our data. Variant chrX-56265420-A-G is described in ClinVar as Benign. ClinVar VariationId is 211311.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 136 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF8	NM_007250.5 link	c.322A>G	p.Ile108Val	missense_variant	Exon 3 of 6	ENST00000468660.6	NP_009181.2	O95600-1A0A024R9X4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF8	ENST00000468660.6 link	c.322A>G	p.Ile108Val	missense_variant	Exon 3 of 6	1	NM_007250.5	ENSP00000417303.1		O95600-1

Frequencies

GnomAD3 genomes

AF:

0.00376

AC:

419

AN:

111446

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000880

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000859

Gnomad ASJ

AF:

0.000756

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00190

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00590

Gnomad OTH

AF:

0.000666

GnomAD2 exomes

AF:

0.00444

AC:

811

AN:

182849

AF XY:

0.00461

show subpopulations

Gnomad AFR exome

AF:

0.000988

Gnomad AMR exome

AF:

0.000731

Gnomad ASJ exome

AF:

0.000671

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0115

Gnomad NFE exome

AF:

0.00674

Gnomad OTH exome

AF:

0.00398

GnomAD4 exome

AF:

0.00655

AC:

7189

AN:

1097891

Hom.:

Cov.:

AF XY:

0.00650

AC XY:

2363

AN XY:

363275

show subpopulations

African (AFR)

AF:

0.000682

AC:

AN:

26396

American (AMR)

AF:

0.000625

AC:

AN:

35175

Ashkenazi Jewish (ASJ)

AF:

0.000568

AC:

AN:

19377

East Asian (EAS)

AF:

0.00

AC:

AN:

30201

South Asian (SAS)

AF:

0.00137

AC:

AN:

54119

European-Finnish (FIN)

AF:

0.00982

AC:

398

AN:

40520

Middle Eastern (MID)

AF:

0.000484

AC:

AN:

4133

European-Non Finnish (NFE)

AF:

0.00767

AC:

6454

AN:

841880

Other (OTH)

AF:

0.00456

AC:

210

AN:

46090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

289

579

868

1158

1447

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

262

524

786

1048

1310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00376

AC:

419

AN:

111500

Hom.:

Cov.:

AF XY:

0.00403

AC XY:

136

AN XY:

33718

show subpopulations

African (AFR)

AF:

0.000878

AC:

AN:

30749

American (AMR)

AF:

0.000857

AC:

AN:

10496

Ashkenazi Jewish (ASJ)

AF:

0.000756

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3550

South Asian (SAS)

AF:

0.00191

AC:

AN:

2620

European-Finnish (FIN)

AF:

0.0103

AC:

AN:

5999

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.00590

AC:

313

AN:

53019

Other (OTH)

AF:

0.000658

AC:

AN:

1520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00471

Hom.:

Bravo

AF:

0.00290

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00450

AC:

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00580

AC:

ExAC

AF:

0.00461

AC:

560

EpiCase

AF:

0.00633

EpiControl

AF:

0.00612

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Aug 19, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 20, 2017

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.068

(source)

DANN

Benign

0.21

DEOGEN2

Benign

0.066

.;T;.

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.62

T;T;T

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.26

N;N;.

PhyloP100

-0.35

PrimateAI

Benign

0.40

PROVEAN

Benign

0.34

N;N;.

REVEL

Benign

0.0090

Sift

Benign

1.0

T;T;.

Sift4G

Benign

1.0

T;T;.

Polyphen

0.0

.;B;.

Vest4

0.032

MVP

0.44

MPC

0.078

ClinPred

0.00014

GERP RS

-0.93

Varity_R

0.033

gMVP

0.082

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.29

Position offset: -1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over