rs1057516362
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_000187.4(HGD):c.31_32delinsATT(p.Gly11IlefsTer3) variant causes a frameshift change. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. G11G) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Consequence
HGD
NM_000187.4 frameshift
NM_000187.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.85
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 Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 372 pathogenic variants in the truncated region.
PP5
?
Variant 3-120675847-CC-AAT is Pathogenic according to our data. Variant chr3-120675847-CC-AAT is described in ClinVar as [Likely_pathogenic]. Clinvar id is 370267.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HGD | NM_000187.4 | c.31_32delinsATT | p.Gly11IlefsTer3 | frameshift_variant | 2/14 | ENST00000283871.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HGD | ENST00000283871.10 | c.31_32delinsATT | p.Gly11IlefsTer3 | frameshift_variant | 2/14 | 1 | NM_000187.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
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 AKU patient in PMID:9529363. It has been submitted to the HGD gene mutation database (http://hgddatabase.cvtisr.sk/, DB-ID: AKU_00005). - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Dec 31, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at