X-73447453-C-G

Variant names:

• chrX-73447453-C-G
• rs145092385
• NM_005193.2:c.200C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005193.2(CDX4):​c.200C>G​(p.Pro67Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,762 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P67A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: CDX4 NM_005193.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23632494).

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.200C>G	p.Pro67Arg	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.200C>G	p.Pro67Arg	missense	Exon 1 of 3	ENSP00000362613.1	O14627
	CDX4	ENST00000911265.1		c.200C>G	p.Pro67Arg	missense	Exon 1 of 4	ENSP00000581324.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.00000547 AC: 1 AN: 182732 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 9.11e-7 AC: 1 AN: 1097762 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363136

African (AFR) AF: 0.00 AC: 0 AN: 26397

American (AMR) AF: 0.0000284 AC: 1 AN: 35196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19379

East Asian (EAS) AF: 0.00 AC: 0 AN: 30200

South Asian (SAS) AF: 0.00 AC: 0 AN: 54115

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841748

Other (OTH) AF: 0.00 AC: 0 AN: 46073

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 133

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	9.3
DANN	Benign	0.74
DEOGEN2	Benign	0.14	T
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.3
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.12
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.044	D
Polyphen		0.061	B
Vest4		0.26
MutPred		0.55		Gain of MoRF binding (P = 0.0267)
MVP		0.69
MPC		0.28
ClinPred		0.13	T
GERP RS		0.66
PromoterAI		-0.0066	Neutral
Varity_R		0.099
gMVP		0.38
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs145092385; hg19: chrX-72667289;