Genetic Variant NM_005193.2:c.200C>A (chrX-73447453-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P67A) has been classified as Uncertain significance.

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

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 710287.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 42 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005193.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDX4	NM_005193.2	MANE Select	c.200C>A	p.Pro67Gln	missense	Exon 1 of 3	NP_005184.1	O14627

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDX4	ENST00000373514.3	TSL:1 MANE Select	c.200C>A	p.Pro67Gln	missense	Exon 1 of 3	ENSP00000362613.1	O14627
	CDX4	ENST00000911265.1		c.200C>A	p.Pro67Gln	missense	Exon 1 of 4	ENSP00000581324.1

Frequencies

GnomAD3 genomes

AF:

0.00173

AC:

193

AN:

111798

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00144

AC:

263

AN:

182732

AF XY:

0.00129

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 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

African (AFR)

AF:

0.000379

AC:

AN:

26397

American (AMR)

AF:

0.000313

AC:

AN:

35196

Ashkenazi Jewish (ASJ)

AF:

0.000413

AC:

AN:

19379

East Asian (EAS)

AF:

0.00

AC:

AN:

30200

South Asian (SAS)

AF:

0.000684

AC:

AN:

54115

European-Finnish (FIN)

AF:

0.00101

AC:

AN:

40520

Middle Eastern (MID)

AF:

0.000484

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.00332

AC:

2798

AN:

841748

Other (OTH)

AF:

0.00282

AC:

130

AN:

46073

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

120

240

360

480

600

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<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:

0.00173

AC:

193

AN:

111850

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

AN XY:

34028

show subpopulations

African (AFR)

AF:

0.000584

AC:

AN:

30833

American (AMR)

AF:

0.000187

AC:

AN:

10667

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2648

East Asian (EAS)

AF:

0.00

AC:

AN:

3499

South Asian (SAS)

AF:

0.000379

AC:

AN:

2636

European-Finnish (FIN)

AF:

0.000164

AC:

AN:

6098

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00315

AC:

167

AN:

53058

Other (OTH)

AF:

0.000661

AC:

AN:

1512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.00263

Hom.:

133

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.26

(source)

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

PhyloP100

1.3

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

PromoterAI

-0.0098

Neutral

(source)

Varity_R

0.047

gMVP

0.37

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over