Variant X-56265323-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_007250.5(KLF8):c.225G>T(p.Leu75Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,205,801 control chromosomes in the GnomAD database, including 17 homozygotes. There are 470 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 9 hom., 216 hem., cov: 22)

Exomes 𝑓: 0.00084 ( 8 hom. 254 hem. )

Consequence

KLF8
NM_007250.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.323

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:

KLF8 (HGNC:):

KLF8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003017038).

BP6

Variant X-56265323-G-T is Benign according to our data. Variant chrX-56265323-G-T is described in ClinVar as [Benign]. Clinvar id is 786706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00792 (878/110901) while in subpopulation AFR AF= 0.0276 (841/30465). AF 95% confidence interval is 0.0261. There are 9 homozygotes in gnomad4. There are 216 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF8	NM_007250.5 linkuse as main transcript	c.225G>T	p.Leu75Phe	missense_variant	3/6	ENST00000468660.6	NP_009181.2	O95600-1A0A024R9X4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF8	ENST00000468660.6 linkuse as main transcript	c.225G>T	p.Leu75Phe	missense_variant	3/6	1	NM_007250.5	ENSP00000417303.1		O95600-1

Frequencies

GnomAD3 genomes

AF:

0.00790

AC:

876

AN:

110846

Hom.:

Cov.:

AF XY:

0.00644

AC XY:

213

AN XY:

33060

show subpopulations

Gnomad AFR

AF:

0.0276

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00231

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:

0.0000378

Gnomad OTH

AF:

0.00744

GnomAD3 exomes

AF:

0.00225

AC:

391

AN:

174040

Hom.:

AF XY:

0.00116

AC XY:

AN XY:

59558

show subpopulations

Gnomad AFR exome

AF:

0.0278

Gnomad AMR exome

AF:

0.00143

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000560

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000131

Gnomad OTH exome

AF:

0.000688

GnomAD4 exome

AF:

0.000845

AC:

925

AN:

1094900

Hom.:

Cov.:

AF XY:

0.000704

AC XY:

254

AN XY:

360622

show subpopulations

Gnomad4 AFR exome

AF:

0.0291

Gnomad4 AMR exome

AF:

0.00141

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000560

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000214

Gnomad4 OTH exome

AF:

0.00185

GnomAD4 genome

AF:

0.00792

AC:

878

AN:

110901

Hom.:

Cov.:

AF XY:

0.00652

AC XY:

216

AN XY:

33125

show subpopulations

Gnomad4 AFR

AF:

0.0276

Gnomad4 AMR

AF:

0.00230

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000378

Gnomad4 OTH

AF:

0.00734

Alfa

AF:

0.000547

Hom.:

Bravo

AF:

0.00894

ESP6500AA

AF:

0.0269

AC:

103

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00233

AC:

283

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

.;T;.

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.87

D;D;D

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Pathogenic

3.0

M;M;.

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.5

D;N;.

REVEL

Benign

0.11

Sift

Uncertain

0.0040

D;D;.

Sift4G

Uncertain

0.042

D;T;.

Polyphen

1.0

.;D;.

Vest4

0.22

MutPred

0.32

Gain of catalytic residue at L75 (P = 0.0048);Gain of catalytic residue at L75 (P = 0.0048);.;

MVP

0.90

MPC

0.51

ClinPred

0.074

GERP RS

2.9

Varity_R

0.31

gMVP

0.19

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

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