CXXC4 p.Gly130Gly

Variant names:

• chr4-104491412-C-C
• NM_025212.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr4-104491413--
• chr4-104491413-A-G
• chr4-104491413-A-T
• chr4-104491413-A-C

Variant summary

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

The NM_025212.4(CXXC4):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: CXXC4 NM_025212.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249
• Publications: 0 publications found

Genes affected

CXXC4 (HGNC:24593): (CXXC finger protein 4) This gene encodes a CXXC-type zinc finger domain-containing protein that functions as an antagonist of the canonical wingless/integrated signaling pathway. The encoded protein negatively regulates wingless/integrated signaling through interaction with the post synaptic density protein/ Drosophila disc large tumor suppressor/ zonula occludens-1 protein domain of Dishevelled, a scaffolding protein required for the stabilization of the transcriptional co-activator beta-catenin. In addition, the CXXC domain of this protein has been shown to bind unmethylated CpG dinucleotides, localize to promoters and CpG islands, and interact with the catalytic domain of methylcytosine dioxygenase ten-eleven-translocation 2, an iron and alpha-ketoglutarate-dependent dioxygenase that modifies the methylation status of DNA. In humans, a mutation in this gene has been associated with development of malignant renal cell carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

CXXC4-AS1 (HGNC:41054): (CXXC4 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025212.4. 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
	CXXC4	NM_025212.4	MANE Select	c.		exon_region	Exon 2 of 3	NP_079488.2	J9JIF5
	CXXC4	NM_001440652.1		c.		exon_region	Exon 3 of 4	NP_001427581.1
	CXXC4	NR_132741.2		n.		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXXC4	ENST00000394767.3	TSL:5 MANE Select	c.		exon_region	Exon 2 of 3	ENSP00000378248.2	J9JIF5
	CXXC4	ENST00000466963.1	TSL:1	n.		intron	N/A
	CXXC4	ENST00000698535.1		c.		exon_region	Exon 2 of 2	ENSP00000513781.1	A0A8V8TLX0

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 14

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-105412569;