chrX-73453658-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_005193.2(CDX4):c.644G>C(p.Arg215Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,198,868 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., 3 hem., cov: 23)
Exomes 𝑓: 0.000013 ( 0 hom. 5 hem. )
Consequence
CDX4
NM_005193.2 missense
NM_005193.2 missense
Scores
13
1
3
Clinical Significance
Conservation
PhyloP100: 8.74
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.898
BS2
?
High Hemizygotes in GnomAd at 3 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDX4 | NM_005193.2 | c.644G>C | p.Arg215Thr | missense_variant | 2/3 | ENST00000373514.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDX4 | ENST00000373514.3 | c.644G>C | p.Arg215Thr | missense_variant | 2/3 | 1 | NM_005193.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000108 AC: 12AN: 111406Hom.: 0 Cov.: 23 AF XY: 0.0000892 AC XY: 3AN XY: 33630
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GnomAD3 exomes AF: 0.0000114 AC: 2AN: 174697Hom.: 0 AF XY: 0.0000167 AC XY: 1AN XY: 59865
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GnomAD4 exome AF: 0.0000129 AC: 14AN: 1087462Hom.: 0 Cov.: 27 AF XY: 0.0000141 AC XY: 5AN XY: 353710
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GnomAD4 genome ? AF: 0.000108 AC: 12AN: 111406Hom.: 0 Cov.: 23 AF XY: 0.0000892 AC XY: 3AN XY: 33630
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 24, 2022 | The c.644G>C (p.R215T) alteration is located in exon 2 (coding exon 2) of the CDX4 gene. This alteration results from a G to C substitution at nucleotide position 644, causing the arginine (R) at amino acid position 215 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Pathogenic
D
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0172);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at