Variant X-73447453-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005193.2(CDX4):c.200C>A(p.Pro67Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00267 in 1,209,612 control chromosomes in the GnomAD database, including 6 homozygotes. There are 954 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., 42 hem., cov: 22)

Exomes 𝑓: 0.0028 ( 6 hom. 912 hem. )

Consequence

CDX4
NM_005193.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.34

Variant links:

Genes affected

CDX4 (HGNC:1808): (caudal type homeobox 4) This gene encodes a member of a small subfamily of homeobox containing transcription factors. The encoded protein may regulate homeobox gene expression during anteroposterior patterning and hematopoiesis. [provided by RefSeq, Aug 2012]

CDX4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055456758).

BP6

Variant X-73447453-C-A is Benign according to our data. Variant chrX-73447453-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 710287.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd at 42 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDX4	NM_005193.2 linkuse as main transcript	c.200C>A	p.Pro67Gln	missense_variant	1/3	ENST00000373514.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDX4	ENST00000373514.3 linkuse as main transcript	c.200C>A	p.Pro67Gln	missense_variant	1/3	1	NM_005193.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00173

AC:

193

AN:

111798

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

33966

show subpopulations

Gnomad AFR

AF:

0.000585

Gnomad AMI

AF:

0.00441

Gnomad AMR

AF:

0.000188

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000378

Gnomad FIN

AF:

0.000164

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00315

Gnomad OTH

AF:

0.000670

GnomAD3 exomes

AF:

0.00144

AC:

263

AN:

182732

Hom.:

AF XY:

0.00129

AC XY:

AN XY:

67304

show subpopulations

Gnomad AFR exome

AF:

0.000533

Gnomad AMR exome

AF:

0.000292

Gnomad ASJ exome

AF:

0.000402

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000579

Gnomad FIN exome

AF:

0.000565

Gnomad NFE exome

AF:

0.00271

Gnomad OTH exome

AF:

0.000886

GnomAD4 exome

AF:

0.00277

AC:

3037

AN:

1097762

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

912

AN XY:

363136

show subpopulations

Gnomad4 AFR exome

AF:

0.000379

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.000413

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000684

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.00332

Gnomad4 OTH exome

AF:

0.00282

GnomAD4 genome

AF:

0.00173

AC:

193

AN:

111850

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

AN XY:

34028

show subpopulations

Gnomad4 AFR

AF:

0.000584

Gnomad4 AMR

AF:

0.000187

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000379

Gnomad4 FIN

AF:

0.000164

Gnomad4 NFE

AF:

0.00315

Gnomad4 OTH

AF:

0.000661

Alfa

AF:

0.00277

Hom.:

129

Bravo

AF:

0.00146

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00312

AC:

ESP6500AA

AF:

0.00156

AC:

ESP6500EA

AF:

0.00253

AC:

ExAC

AF:

0.00157

AC:

191

EpiCase

AF:

0.00251

EpiControl

AF:

0.00315

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.82

Cadd

Benign

0.26

Dann

Benign

0.14

DEOGEN2

Benign

0.049

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.53

M_CAP

Benign

0.0026

MetaRNN

Benign

0.0055

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.58

MutationTaster

Benign

1.0

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.24

REVEL

Benign

0.080

Sift

Benign

0.75

Sift4G

Benign

0.70

Polyphen

0.0

Vest4

0.099

MVP

0.64

MPC

0.11

ClinPred

0.00030

GERP RS

0.66

Varity_R

0.047

gMVP

0.37

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