CP p.Tyr857Tyr

Variant names:

• chr3-149179645-C-C
• NM_000096.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr3-149179646--
• chr3-149179646-G-A

Variant summary

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

The NM_000096.4(CP):​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: 32)
• Consequence: CP NM_000096.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• Publications: 0 publications found

Genes affected

CP (HGNC:2295): (ceruloplasmin) The protein encoded by this gene is a metalloprotein that binds most of the copper in plasma and is involved in the peroxidation of Fe(II)transferrin to Fe(III) transferrin. Mutations in this gene cause aceruloplasminemia, which results in iron accumulation and tissue damage, and is associated with diabetes and neurologic abnormalities. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene. [provided by RefSeq, Feb 2012]

CP Gene-Disease associations (from GenCC):

• aceruloplasminemia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
• disorder of iron metabolism and transport

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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_000096.4. 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
	CP	NM_000096.4	MANE Select	c.		exon_region	Exon 15 of 19	NP_000087.2	P00450
	CP	NR_046371.2		n.		exon_region	Exon 14 of 18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CP	ENST00000264613.11	TSL:1 MANE Select	c.		exon_region	Exon 15 of 19	ENSP00000264613.6	P00450
	CP	ENST00000494544.1	TSL:1	c.		exon_region	Exon 12 of 16	ENSP00000420545.1	H7C5R1
	CP	ENST00000460674.5	TSL:1	n.		exon_region	Exon 1 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.014

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: chr3-148897432;