chr3-149185282-GTGGGGAATAATCCCATTCCACCTCCACTGCTGCGATATAGTATGTCCTCTCTCCCAGGTAGAAGGTGGAATCCTCAGACTGCCGCCTGCATTGGTTCACAGTATATTTTTGCTTCATGCCGCCTGTGTAATGATCAGTTGTAAGGCATTCAACATTAAAAGTCCCTGGAGTGGTAAATAAGAAAACATGTCACTTCTTTGCTAGTGCCCTCTGGGGCTCTCCACCTTCCTCAGAATTA-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP3PP5
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. The variant was absent in control chromosomes in GnomAD project. 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
NM_000096.4 splice_acceptor, coding_sequence, intron
Scores
Not classified
Clinical Significance
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Splicing variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
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
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
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 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at