Variant X-73454407-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_005193.2(CDX4):c.677C>G(p.Ala226Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000731 in 1,094,785 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000073 ( 0 hom. 1 hem. )

Consequence

CDX4
NM_005193.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.01

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 made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.912

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDX4	NM_005193.2 linkuse as main transcript	c.677C>G	p.Ala226Gly	missense_variant	3/3	ENST00000373514.3	NP_005184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDX4	ENST00000373514.3 linkuse as main transcript	c.677C>G	p.Ala226Gly	missense_variant	3/3	1	NM_005193.2	ENSP00000362613	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000390

AC:

AN:

179459

Hom.:

AF XY:

0.0000156

AC XY:

AN XY:

64263

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000258

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000731

AC:

AN:

1094785

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

360417

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000228

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

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

Dec 16, 2022

The c.677C>G (p.A226G) alteration is located in exon 3 (coding exon 3) of the CDX4 gene. This alteration results from a C to G substitution at nucleotide position 677, causing the alanine (A) at amino acid position 226 to be replaced by a glycine (G). 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

Pathogenic

0.81

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Pathogenic

0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.94

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

M_CAP

Pathogenic

0.58

MetaRNN

Pathogenic

0.91

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.5

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.9

REVEL

Pathogenic

0.91

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.73

MutPred

0.71

Gain of disorder (P = 0.0904);

MVP

0.99

MPC

0.55

ClinPred

0.87

GERP RS

4.0

Varity_R

0.91

gMVP

0.48

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over