Genetic Variant NM_005193.2:c.166T>C (chrX-73447419-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005193.2(CDX4):c.166T>C(p.Tyr56His) variant causes a missense change. The variant allele was found at a frequency of 0.00000331 in 1,207,973 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

CDX4
NM_005193.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.62

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.166T>C	p.Tyr56His	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.166T>C	p.Tyr56His	missense	Exon 1 of 3	ENSP00000362613.1	O14627
	CDX4	ENST00000911265.1		c.166T>C	p.Tyr56His	missense	Exon 1 of 4	ENSP00000581324.1

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

111243

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000189

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1096730

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362122

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26365

American (AMR)

AF:

0.0000284

AC:

AN:

35186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19373

East Asian (EAS)

AF:

0.00

AC:

AN:

30191

South Asian (SAS)

AF:

0.00

AC:

AN:

54034

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40503

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

840907

Other (OTH)

AF:

0.00

AC:

AN:

46039

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000180

AC:

AN:

111243

Hom.:

Cov.:

AF XY:

0.0000299

AC XY:

AN XY:

33465

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30548

American (AMR)

AF:

0.000189

AC:

AN:

10597

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3494

South Asian (SAS)

AF:

0.00

AC:

AN:

2588

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6031

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52939

Other (OTH)

AF:

0.00

AC:

AN:

1480

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000718

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

0.17

BayesDel_addAF

Benign

0.0073

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.83

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.72

MetaSVM

Uncertain

-0.18

MutationAssessor

Pathogenic

3.1

PhyloP100

4.6

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.49

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.42

MutPred

0.72

Loss of phosphorylation at Y56 (P = 0.0614)

MVP

0.68

MPC

0.62

ClinPred

0.97

GERP RS

2.6

PromoterAI

0.00070

Neutral

(source)

Varity_R

0.53

gMVP

0.56

Mutation Taster

=93/7

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over