dbSNP rs1020672167: CDX4:p.His52Tyr (chrX-73447407-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_005193.2(CDX4):c.154C>T(p.His52Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000232 in 1,209,287 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000025 ( 0 hom. 12 hem. )

Consequence

CDX4
NM_005193.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.35

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 12 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.154C>T	p.His52Tyr	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.154C>T	p.His52Tyr	missense	Exon 1 of 3	ENSP00000362613.1	O14627
	CDX4	ENST00000911265.1		c.154C>T	p.His52Tyr	missense	Exon 1 of 4	ENSP00000581324.1

Frequencies

GnomAD3 genomes

AF:

0.00000896

AC:

AN:

111593

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1097694

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

363066

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26385

American (AMR)

AF:

0.00

AC:

AN:

35180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19378

East Asian (EAS)

AF:

0.00

AC:

AN:

30196

South Asian (SAS)

AF:

0.00

AC:

AN:

54067

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40483

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.0000297

AC:

AN:

841804

Other (OTH)

AF:

0.0000434

AC:

AN:

46067

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00000896

AC:

AN:

111593

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33757

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30704

American (AMR)

AF:

0.00

AC:

AN:

10622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3507

South Asian (SAS)

AF:

0.00

AC:

AN:

2595

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6080

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

53030

Other (OTH)

AF:

0.00

AC:

AN:

1485

Alfa

AF:

0.000187

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0077

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

PhyloP100

4.4

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.25

Sift

Uncertain

0.013

Sift4G

Uncertain

0.015

Polyphen

0.98

Vest4

0.24

MutPred

0.65

Gain of phosphorylation at H52 (P = 0.0247)

MVP

0.34

MPC

0.44

ClinPred

0.97

GERP RS

2.5

PromoterAI

0.017

Neutral

(source)

Varity_R

0.22

gMVP

0.55

Mutation Taster

=98/2

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over