chr8-31032014-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001323311.2(PURG):​c.769G>C​(p.Asp257His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PURG
NM_001323311.2 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.81

Publications

0 publications found
Variant links:
Genes affected
PURG (HGNC:17930): (purine rich element binding protein G) The exact function of this gene is not known, however, its encoded product is highly similar to purine-rich element binding protein A. The latter is a DNA-binding protein which binds preferentially to the single strand of the purine-rich element termed PUR, and has been implicated in the control of both DNA replication and transcription. This gene lies in close proximity to the Werner syndrome gene, but on the opposite strand, on chromosome 8p11. [provided by RefSeq, Apr 2016]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22876272).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PURGNM_001323311.2 linkc.769G>C p.Asp257His missense_variant Exon 2 of 2 ENST00000523392.2 NP_001310240.1 Q9UJV8-1
PURGNM_013357.2 linkc.769G>C p.Asp257His missense_variant Exon 1 of 1 NP_037489.1 Q9UJV8-1
PURGNM_001015508.3 linkc.769G>C p.Asp257His missense_variant Exon 1 of 2 NP_001015508.1 Q9UJV8-2
PURGNM_001323312.2 linkc.769G>C p.Asp257His missense_variant Exon 2 of 3 NP_001310241.1 Q9UJV8-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PURGENST00000523392.2 linkc.769G>C p.Asp257His missense_variant Exon 2 of 2 3 NM_001323311.2 ENSP00000466881.2 Q9UJV8-1K7ENC1
PURGENST00000339382.3 linkc.769G>C p.Asp257His missense_variant Exon 1 of 2 1 ENSP00000345168.2 Q9UJV8-2
PURGENST00000475541.2 linkc.769G>C p.Asp257His missense_variant Exon 1 of 1 6 ENSP00000418721.1 Q9UJV8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251464
AF XY:
0.00000736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461860
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727236
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.0000224
AC:
1
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86240
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53406
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1112012
Other (OTH)
AF:
0.00
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 06, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.769G>C (p.D257H) alteration is located in exon 1 (coding exon 1) of the PURG gene. This alteration results from a G to C substitution at nucleotide position 769, causing the aspartic acid (D) at amino acid position 257 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.46
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.18
.;T
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.23
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L;L
PhyloP100
4.8
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.12
Sift
Uncertain
0.020
D;D
Sift4G
Benign
0.17
T;T
Polyphen
0.90
P;P
Vest4
0.18
MutPred
0.37
Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP
0.22
MPC
2.1
ClinPred
0.82
D
GERP RS
5.3
Varity_R
0.16
gMVP
0.46
Mutation Taster
=74/26
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs770025349; hg19: chr8-30889530; API