rs1553721650
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The NM_000187.4(HGD):c.16-272_87+305del variant causes a exon loss, splice acceptor, splice donor, splice region, intron change involving the alteration of a non-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
HGD
NM_000187.4 exon_loss, splice_acceptor, splice_donor, splice_region, intron
NM_000187.4 exon_loss, splice_acceptor, splice_donor, splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.666
Genes affected
HGD (HGNC:4892): (homogentisate 1,2-dioxygenase) This gene encodes the enzyme homogentisate 1,2 dioxygenase. This enzyme is involved in the catabolism of the amino acids tyrosine and phenylalanine. Mutations in this gene are the cause of the autosomal recessive metabolism disorder alkaptonuria.[provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.053064276 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-120675486-AATGCTCACATCCATGGTGTTCAAGGGGAATATGAGGGATTCTCTTTAACTCTGGATTTTTGGGGATCCTACTGGAAACCCTACAGTTAATTTCACTAGTTTGGATTGGCTGCTGTGCCACCAATCCAATTTTAATCTTTGTGTTGTCATTGCTCTGTATCTTCATTGCCCCTATGACTTGGGAAACCTCTAGACAGTTCACAGGCTAGATTGGAAGAGCCACGGTGGGTGGAGGCACTTTGGCCTGAAAGCTAGTCATCCAGGAATAGGATTCAGAGCTCTTCTAAGCACTTTATTTGCTCATACCTGTCCTTCTGGCAGGGAACCTGGGCAGCGAGGATCCTCTGAAGAACACTCATTCCCAAATCCAGAAATGTACTGTAGGTGACAAAGACACAAATGCCACCATTAGCAGGATTTAAAGAGCATTTCAGAAAATTGGCAGTTTACTAAGGTAAGAATTTCTATATGGACCTATGTTTGTGTATGATGTTCCACATATAATATCTTTACTGTGTCTTGACATATGAATCATTTAGGGAAGACAATATGGTTTCTGTGAATTTTAAAGACTTCTAATTAATCAGAAGAGTGCTGGATATTGCATAGACTTCTCCACCCTTAGCTGTACTTAGCTGATTTGTGGGTCT-A is Pathogenic according to our data. Variant chr3-120675486-AATGCTCACATCCATGGTGTTCAAGGGGAATATGAGGGATTCTCTTTAACTCTGGATTTTTGGGGATCCTACTGGAAACCCTACAGTTAATTTCACTAGTTTGGATTGGCTGCTGTGCCACCAATCCAATTTTAATCTTTGTGTTGTCATTGCTCTGTATCTTCATTGCCCCTATGACTTGGGAAACCTCTAGACAGTTCACAGGCTAGATTGGAAGAGCCACGGTGGGTGGAGGCACTTTGGCCTGAAAGCTAGTCATCCAGGAATAGGATTCAGAGCTCTTCTAAGCACTTTATTTGCTCATACCTGTCCTTCTGGCAGGGAACCTGGGCAGCGAGGATCCTCTGAAGAACACTCATTCCCAAATCCAGAAATGTACTGTAGGTGACAAAGACACAAATGCCACCATTAGCAGGATTTAAAGAGCATTTCAGAAAATTGGCAGTTTACTAAGGTAAGAATTTCTATATGGACCTATGTTTGTGTATGATGTTCCACATATAATATCTTTACTGTGTCTTGACATATGAATCATTTAGGGAAGACAATATGGTTTCTGTGAATTTTAAAGACTTCTAATTAATCAGAAGAGTGCTGGATATTGCATAGACTTCTCCACCCTTAGCTGTACTTAGCTGATTTGTGGGTCT-A is described in ClinVar as [Pathogenic]. Clinvar id is 156275.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HGD | NM_000187.4 | c.16-272_87+305del | exon_loss_variant, splice_acceptor_variant, splice_donor_variant, splice_region_variant, intron_variant | 2/14 | ENST00000283871.10 | NP_000178.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HGD | ENST00000283871.10 | c.16-272_87+305del | exon_loss_variant, splice_acceptor_variant, splice_donor_variant, splice_region_variant, intron_variant | 2/14 | 1 | NM_000187.4 | ENSP00000283871.5 |
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:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Alkaptonuria Pathogenic:2
Pathogenic, no assertion criteria provided | research | Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences | - | The variant was originally described in PMID:25233259. It has been submitted to the HGD gene mutation database (http://hgddatabase.cvtisr.sk/, DB-ID: AKU_00164). - |
Pathogenic, no assertion criteria provided | research | Chehab Lab, University of California, San Francisco | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at