chr5-140114209-C-T
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_005859.5(PURA):c.28C>T(p.Gln10*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000127 in 787,418 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 (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000013 ( 0 hom. )
Consequence
PURA
NM_005859.5 stop_gained
NM_005859.5 stop_gained
Scores
3
3
Clinical Significance
Conservation
PhyloP100: 5.42
Publications
0 publications found
Genes affected
PURA (HGNC:9701): (purine rich element binding protein A) This gene product is a sequence-specific, single-stranded DNA-binding protein. It binds preferentially to the single strand of the purine-rich element termed PUR, which is present at origins of replication and in gene flanking regions in a variety of eukaryotes from yeasts through humans. Thus, it is implicated in the control of both DNA replication and transcription. Deletion of this gene has been associated with myelodysplastic syndrome and acute myelogenous leukemia. [provided by RefSeq, Jul 2008]
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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 is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 200 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 5-140114209-C-T is Pathogenic according to our data. Variant chr5-140114209-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 3336937.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_005859.5. 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 |
|---|---|---|---|---|---|---|---|---|---|
| PURA | NM_005859.5 | MANE Select | c.28C>T | p.Gln10* | stop_gained | Exon 1 of 1 | NP_005850.1 | Q00577 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PURA | ENST00000331327.5 | TSL:6 MANE Select | c.28C>T | p.Gln10* | stop_gained | Exon 1 of 1 | ENSP00000332706.3 | Q00577 | |
| PURA | ENST00000651386.1 | c.28C>T | p.Gln10* | stop_gained | Exon 2 of 2 | ENSP00000499133.1 | Q00577 | ||
| PURA | ENST00000505703.2 | TSL:3 | c.28C>T | p.Gln10* | stop_gained | Exon 2 of 2 | ENSP00000498560.1 | A0A494C0H6 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 0.00000127 AC: 1AN: 787418Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0AN XY: 380394 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
787418
Hom.:
Cov.:
10
AF XY:
AC XY:
0
AN XY:
380394
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
16260
American (AMR)
AF:
AC:
0
AN:
6690
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
10456
East Asian (EAS)
AF:
AC:
0
AN:
21252
South Asian (SAS)
AF:
AC:
0
AN:
14420
European-Finnish (FIN)
AF:
AC:
0
AN:
19578
Middle Eastern (MID)
AF:
AC:
0
AN:
2312
European-Non Finnish (NFE)
AF:
AC:
1
AN:
664358
Other (OTH)
AF:
AC:
0
AN:
32092
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
ClinVar submissions
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
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
PhyloP100
Vest4
GERP RS
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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