chrX-73447734-C-G

Variant names:

• chrX-73447734-C-G
• rs752673817
• NM_005193.2:c.481C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005193.2(CDX4):​c.481C>G​(p.Arg161Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000938 in 1,066,225 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.4e-7 (0 hom. 0 hem.)
• Consequence: CDX4 NM_005193.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.76
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32874575).

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.481C>G	p.Arg161Gly	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.481C>G	p.Arg161Gly	missense	Exon 1 of 3	ENSP00000362613.1	O14627
	CDX4	ENST00000911265.1		c.481C>G	p.Arg161Gly	missense	Exon 1 of 4	ENSP00000581324.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.38e-7 AC: 1 AN: 1066225 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 344167

African (AFR) AF: 0.00 AC: 0 AN: 25892

American (AMR) AF: 0.00 AC: 0 AN: 33319

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17837

East Asian (EAS) AF: 0.00 AC: 0 AN: 29918

South Asian (SAS) AF: 0.00 AC: 0 AN: 50784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30135

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4007

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 829318

Other (OTH) AF: 0.0000222 AC: 1 AN: 45015

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.8
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.14
Sift	Benign	0.094	T
Sift4G	Benign	0.12	T
Polyphen		0.029	B
Vest4		0.35
MutPred		0.66		Loss of solvent accessibility (P = 0.0329)
MVP		0.93
MPC		0.62
ClinPred		0.96	D
GERP RS		2.4
Varity_R		0.36
gMVP		0.72
Mutation Taster		=79/21	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: rs752673817; hg19: chrX-72667570;