12-21437676-CCA-C
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
The NM_024854.5(PYROXD1):c.-54_-53del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,550,036 control chromosomes in the GnomAD database, including 36 homozygotes. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0079 ( 17 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 19 hom. )
Consequence
PYROXD1
NM_024854.5 5_prime_UTR
NM_024854.5 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -2.38
Genes affected
PYROXD1 (HGNC:26162): (pyridine nucleotide-disulphide oxidoreductase domain 1) This gene encodes a nuclear-cytoplasmic pyridine nucleotide-disulphide reductase (PNDR). PNDRs are flavoproteins that catalyze the pyridine nucleotide-dependent reduction of thiol residues in other proteins. The encoded protein belongs to the class I pyridine nucleotide-disulphide oxidoreductase family but lacks the C-terminal dimerization domain found in other family members and instead has a C-terminal nitrile reductase domain. It localizes to the nucleus and to striated sarcomeric compartments. Naturally occurring mutations in this gene cause early-onset myopathy with internalized nuclei and myofibrillar disorganization. A pseudogene of this gene has been defined on chromosome 11. [provided by RefSeq, Apr 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP6
?
Variant 12-21437676-CCA-C is Benign according to our data. Variant chr12-21437676-CCA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1301018.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00791 (1205/152258) while in subpopulation AFR AF= 0.0239 (992/41540). AF 95% confidence interval is 0.0226. There are 17 homozygotes in gnomad4. There are 595 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 18 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PYROXD1 | NM_024854.5 | c.-54_-53del | 5_prime_UTR_variant | 1/12 | ENST00000240651.14 | ||
PYROXD1 | NM_001350913.2 | c.-757_-756del | 5_prime_UTR_variant | 1/11 | |||
PYROXD1 | XM_006719153.4 | c.-54_-53del | 5_prime_UTR_variant | 1/8 | |||
PYROXD1 | XM_047429554.1 | c.-54_-53del | 5_prime_UTR_variant | 1/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PYROXD1 | ENST00000240651.14 | c.-54_-53del | 5_prime_UTR_variant | 1/12 | 1 | NM_024854.5 | P1 | ||
PYROXD1 | ENST00000375266.8 | c.-54_-53del | 5_prime_UTR_variant, NMD_transcript_variant | 1/13 | 5 | ||||
PYROXD1 | ENST00000543476.5 | c.-54_-53del | 5_prime_UTR_variant, NMD_transcript_variant | 1/9 | 5 | ||||
PYROXD1 | ENST00000544970.5 | upstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00791 AC: 1203AN: 152140Hom.: 18 Cov.: 32
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GnomAD4 exome AF: 0.00158 AC: 2206AN: 1397778Hom.: 19 AF XY: 0.00146 AC XY: 1015AN XY: 692898
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GnomAD4 genome ? AF: 0.00791 AC: 1205AN: 152258Hom.: 17 Cov.: 32 AF XY: 0.00799 AC XY: 595AN XY: 74450
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at