Variant X-73454526-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005193.2(CDX4):c.796C>T(p.Pro266Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000237 in 1,207,842 control chromosomes in the GnomAD database, including 1 homozygotes. There are 120 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.00025 ( 1 hom. 117 hem. )

Consequence

CDX4
NM_005193.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.41

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013189137).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDX4	NM_005193.2 linkuse as main transcript	c.796C>T	p.Pro266Ser	missense_variant	3/3	ENST00000373514.3	NP_005184.1	O14627

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDX4	ENST00000373514.3 linkuse as main transcript	c.796C>T	p.Pro266Ser	missense_variant	3/3	1	NM_005193.2	ENSP00000362613.1		O14627

Frequencies

GnomAD3 genomes

AF:

0.000117

AC:

AN:

111253

Hom.:

Cov.:

AF XY:

0.0000896

AC XY:

AN XY:

33481

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:

0.00281

Gnomad SAS

AF:

0.00115

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000329

AC:

AN:

182469

Hom.:

AF XY:

0.000433

AC XY:

AN XY:

66995

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00268

Gnomad SAS exome

AF:

0.00122

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000249

AC:

273

AN:

1096538

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

117

AN XY:

362026

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00599

Gnomad4 SAS exome

AF:

0.00131

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.000435

GnomAD4 genome

AF:

0.000117

AC:

AN:

111304

Hom.:

Cov.:

AF XY:

0.0000894

AC XY:

AN XY:

33542

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00282

Gnomad4 SAS

AF:

0.00115

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000982

ExAC

AF:

0.000395

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

Jul 27, 2022

The c.796C>T (p.P266S) alteration is located in exon 3 (coding exon 3) of the CDX4 gene. This alteration results from a C to T substitution at nucleotide position 796, causing the proline (P) at amino acid position 266 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

0.067

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.14

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.50

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.013

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.5

REVEL

Benign

0.18

Sift

Benign

0.075

Sift4G

Benign

0.27

Polyphen

0.76

Vest4

0.024

MVP

0.98

MPC

0.12

ClinPred

0.068

GERP RS

3.0

Varity_R

0.059

gMVP

0.42

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