Variant X-56265420-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 12/21 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:3

Conservation

PhyloP100: -0.354

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 211311.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-56265420-A-G is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 136 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF8	NM_007250.5 linkuse as main transcript	c.322A>G	p.Ile108Val	missense_variant	3/6	ENST00000468660.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF8	ENST00000468660.6 linkuse as main transcript	c.322A>G	p.Ile108Val	missense_variant	3/6	1	NM_007250.5	P1	O95600-1

Frequencies

GnomAD3 genomes

AF:

0.00376

AC:

419

AN:

111446

Hom.:

Cov.:

AF XY:

0.00404

AC XY:

136

AN XY:

33654

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

GnomAD3 exomes

AF:

0.00444

AC:

811

AN:

182849

Hom.:

AF XY:

0.00461

AC XY:

311

AN XY:

67431

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 SAS exome

AF:

0.00110

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

Gnomad4 AFR exome

AF:

0.000682

Gnomad4 AMR exome

AF:

0.000625

Gnomad4 ASJ exome

AF:

0.000568

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00137

Gnomad4 FIN exome

AF:

0.00982

Gnomad4 NFE exome

AF:

0.00767

Gnomad4 OTH exome

AF:

0.00456

GnomAD4 genome

AF:

0.00376

AC:

419

AN:

111500

Hom.:

Cov.:

AF XY:

0.00403

AC XY:

136

AN XY:

33718

show subpopulations

Gnomad4 AFR

AF:

0.000878

Gnomad4 AMR

AF:

0.000857

Gnomad4 ASJ

AF:

0.000756

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00191

Gnomad4 FIN

AF:

0.0103

Gnomad4 NFE

AF:

0.00590

Gnomad4 OTH

AF:

0.000658

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Aug 19, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 20, 2017	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

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

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;.

MutationTaster

Benign

1.0

N;N

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

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

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