NM_002150.3:c.250_253dupGATC
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_002150.3(HPD):c.250_253dupGATC(p.His85ArgfsTer8) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_002150.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HPD | NM_002150.3 | c.250_253dupGATC | p.His85ArgfsTer8 | frameshift_variant | Exon 6 of 14 | ENST00000289004.8 | NP_002141.2 | |
HPD | NM_001171993.2 | c.133_136dupGATC | p.His46ArgfsTer8 | frameshift_variant | Exon 8 of 16 | NP_001165464.1 | ||
TIALD | XR_002957437.2 | n.144_147dupATCG | non_coding_transcript_exon_variant | Exon 1 of 3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HPD | ENST00000289004.8 | c.250_253dupGATC | p.His85ArgfsTer8 | frameshift_variant | Exon 6 of 14 | 1 | NM_002150.3 | ENSP00000289004.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251460Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135916
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461866Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727234
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Tyrosinemia type III;C2931042:Hawkinsinuria Pathogenic:1
This sequence change creates a premature translational stop signal (p.His85Argfs*8) in the HPD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HPD are known to be pathogenic (PMID: 10942115, 23036342). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with HPD-related conditions. For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at