rs118203955
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The ENST00000369037.9(PDSS2):c.964C>T(p.Gln322Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000746 in 1,608,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000076 ( 0 hom. )
Consequence
PDSS2
ENST00000369037.9 stop_gained
ENST00000369037.9 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 6.31
Genes affected
PDSS2 (HGNC:23041): (decaprenyl diphosphate synthase subunit 2) The protein encoded by this gene is an enzyme that synthesizes the prenyl side-chain of coenzyme Q, or ubiquinone, one of the key elements in the respiratory chain. The gene product catalyzes the formation of all trans-polyprenyl pyrophosphates from isopentyl diphosphate in the assembly of polyisoprenoid side chains, the first step in coenzyme Q biosynthesis. Defects in this gene are a cause of coenzyme Q10 deficiency.[provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-107210483-G-A is Pathogenic according to our data. Variant chr6-107210483-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 1200.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PDSS2 | NM_020381.4 | c.964C>T | p.Gln322Ter | stop_gained | 6/8 | ENST00000369037.9 | NP_065114.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PDSS2 | ENST00000369037.9 | c.964C>T | p.Gln322Ter | stop_gained | 6/8 | 1 | NM_020381.4 | ENSP00000358033 | P1 | |
PDSS2 | ENST00000449027.1 | c.139C>T | p.Gln47Ter | stop_gained | 2/3 | 3 | ENSP00000392613 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152096Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251146Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135782
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GnomAD4 exome AF: 0.00000755 AC: 11AN: 1456706Hom.: 0 Cov.: 28 AF XY: 0.00000552 AC XY: 4AN XY: 725116
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152096Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74288
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Coenzyme Q10 deficiency, primary, 3 Pathogenic:1Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 2010 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at