X-73447542-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005193.2(CDX4):​c.289C>T​(p.Pro97Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,209,659 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.0000091 ( 0 hom. 4 hem. )

Consequence

CDX4
NM_005193.2 missense

Scores

8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.52
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDX4NM_005193.2 linkc.289C>T p.Pro97Ser missense_variant Exon 1 of 3 ENST00000373514.3 NP_005184.1 O14627

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDX4ENST00000373514.3 linkc.289C>T p.Pro97Ser missense_variant Exon 1 of 3 1 NM_005193.2 ENSP00000362613.1 O14627

Frequencies

GnomAD3 genomes
AF:
0.0000357
AC:
4
AN:
112037
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34199
show subpopulations
Gnomad AFR
AF:
0.0000324
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:
0.0000565
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000219
AC:
4
AN:
182478
Hom.:
0
AF XY:
0.0000149
AC XY:
1
AN XY:
67128
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000492
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000911
AC:
10
AN:
1097622
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
4
AN XY:
362996
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000107
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
AF:
0.0000357
AC:
4
AN:
112037
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34199
show subpopulations
Gnomad4 AFR
AF:
0.0000324
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000565
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000453
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.289C>T (p.P97S) alteration is located in exon 1 (coding exon 1) of the CDX4 gene. This alteration results from a C to T substitution at nucleotide position 289, causing the proline (P) at amino acid position 97 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.082
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
13
DANN
Uncertain
1.0
DEOGEN2
Benign
0.097
T
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.52
T
M_CAP
Uncertain
0.094
D
MetaRNN
Uncertain
0.47
T
MetaSVM
Uncertain
0.31
D
MutationAssessor
Uncertain
2.6
M
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-0.69
N
REVEL
Uncertain
0.36
Sift
Benign
0.12
T
Sift4G
Benign
0.32
T
Polyphen
0.98
D
Vest4
0.26
MVP
1.0
MPC
0.29
ClinPred
0.30
T
GERP RS
2.6
Varity_R
0.054
gMVP
0.50

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.

Other links and lift over

dbSNP: rs772299390; hg19: chrX-72667378; API