rs2136428332
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_025215.6(PUS1):c.10C>T(p.Gln4*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Q4Q) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PUS1
NM_025215.6 stop_gained
NM_025215.6 stop_gained
Scores
1
2
3
Clinical Significance
Conservation
PhyloP100: 0.0800
Publications
0 publications found
Genes affected
PUS1 (HGNC:15508): (pseudouridine synthase 1) This gene encodes a pseudouridine synthase that converts uridine to pseudouridine once it has been incorporated into an RNA molecule. The encoded enzyme may play an essential role in tRNA function and in stabilizing the secondary and tertiary structure of many RNAs. A mutation in this gene has been linked to mitochondrial myopathy and sideroblastic anemia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Sep 2009]
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 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 57 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 12-131929732-C-T is Pathogenic according to our data. Variant chr12-131929732-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 1361128.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_025215.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PUS1 | NM_025215.6 | MANE Select | c.10C>T | p.Gln4* | stop_gained | Exon 1 of 6 | NP_079491.2 | E5KMT5 | |
| PUS1 | NM_001002019.3 | c.-10-175C>T | intron | N/A | NP_001002019.1 | E5KMT6 | |||
| PUS1 | NM_001002020.3 | c.-10-175C>T | intron | N/A | NP_001002020.1 | E5KMT6 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PUS1 | ENST00000376649.8 | TSL:1 MANE Select | c.10C>T | p.Gln4* | stop_gained | Exon 1 of 6 | ENSP00000365837.3 | Q9Y606-1 | |
| PUS1 | ENST00000443358.6 | TSL:1 | c.-10-175C>T | intron | N/A | ENSP00000392451.2 | Q9Y606-2 | ||
| PUS1 | ENST00000890860.1 | c.10C>T | p.Gln4* | stop_gained | Exon 1 of 6 | ENSP00000560919.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1439204Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 716132
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1439204
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
716132
African (AFR)
AF:
AC:
0
AN:
32586
American (AMR)
AF:
AC:
0
AN:
43950
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25772
East Asian (EAS)
AF:
AC:
0
AN:
38618
South Asian (SAS)
AF:
AC:
0
AN:
84726
European-Finnish (FIN)
AF:
AC:
0
AN:
40516
Middle Eastern (MID)
AF:
AC:
0
AN:
5222
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1107962
Other (OTH)
AF:
AC:
0
AN:
59852
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
PhyloP100
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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