rs1553759167

chr3-149185282-GTGGGGAATAATCCCATTCCACCTCCACTGCTGCGATATAGTATGTCCTCTCTCCCAGGTAGAAGGTGGAATCCTCAGACTGCCGCCTGCATTGGTTCACAGTATATTTTTGCTTCATGCCGCCTGTGTAATGATCAGTTGTAAGGCATTCAACATTAAAAGTCCCTGGAGTGGTAAATAAGAAAACATGTCACTTCTTTGCTAGTGCCCTCTGGGGCTCTCCACCTTCCTCAGAATTA-G

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PP3 PP5

The NM_000096.4(CP):c.2078-74_2241del variant causes a splice acceptor, coding sequence, intron change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CP NM_000096.4 splice_acceptor, coding_sequence, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.13

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]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Splicing variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 3-149185282-GTGGGGAATAATCCCATTCCACCTCCACTGCTGCGATATAGTATGTCCTCTCTCCCAGGTAGAAGGTGGAATCCTCAGACTGCCGCCTGCATTGGTTCACAGTATATTTTTGCTTCATGCCGCCTGTGTAATGATCAGTTGTAAGGCATTCAACATTAAAAGTCCCTGGAGTGGTAAATAAGAAAACATGTCACTTCTTTGCTAGTGCCCTCTGGGGCTCTCCACCTTCCTCAGAATTA-G is Pathogenic according to our data. Variant chr3-149185282-GTGGGGAATAATCCCATTCCACCTCCACTGCTGCGATATAGTATGTCCTCTCTCCCAGGTAGAAGGTGGAATCCTCAGACTGCCGCCTGCATTGGTTCACAGTATATTTTTGCTTCATGCCGCCTGTGTAATGATCAGTTGTAAGGCATTCAACATTAAAAGTCCCTGGAGTGGTAAATAAGAAAACATGTCACTTCTTTGCTAGTGCCCTCTGGGGCTCTCCACCTTCCTCAGAATTA-G is described in ClinVar as [Pathogenic]. Clinvar id is 488149.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CP	NM_000096.4	c.2078-74_2241del		splice_acceptor_variant, coding_sequence_variant, intron_variant	12/19	ENST00000264613.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CP	ENST00000264613.11	c.2078-74_2241del		splice_acceptor_variant, coding_sequence_variant, intron_variant	12/19	1	NM_000096.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Deficiency of ferroxidase Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Dept of Medicine and Surgery, University of Milano-Bicocca

Jan 14, 2015

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1553759167; hg19: chr3-148903069;