rs768857757

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001323311.2(PURG):c.22G>A(p.Gly8Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000834 in 1,438,182 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: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

PURG
NM_001323311.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.78

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]

PURG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10716352).

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PURG	NM_001323311.2 link	c.22G>A	p.Gly8Arg	missense_variant	Exon 2 of 2	ENST00000523392.2	NP_001310240.1	Q9UJV8-1
PURG	NM_013357.2 link	c.22G>A	p.Gly8Arg	missense_variant	Exon 1 of 1		NP_037489.1	Q9UJV8-1
PURG	NM_001015508.3 link	c.22G>A	p.Gly8Arg	missense_variant	Exon 1 of 2		NP_001015508.1	Q9UJV8-2
PURG	NM_001323312.2 link	c.22G>A	p.Gly8Arg	missense_variant	Exon 2 of 3		NP_001310241.1	Q9UJV8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PURG	ENST00000523392.2 link	c.22G>A	p.Gly8Arg	missense_variant	Exon 2 of 2	3	NM_001323311.2	ENSP00000466881.2	Q9UJV8-1K7ENC1
PURG	ENST00000339382.3 link	c.22G>A	p.Gly8Arg	missense_variant	Exon 1 of 2	1		ENSP00000345168.2	Q9UJV8-2
PURG	ENST00000475541.2 link	c.22G>A	p.Gly8Arg	missense_variant	Exon 1 of 1	6		ENSP00000418721.1	Q9UJV8-1

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150918

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000659

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000608

AC:

AN:

82304

AF XY:

0.0000245

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000452

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:

0.00000855

AC:

AN:

1287264

Hom.:

Cov.:

AF XY:

0.00000642

AC XY:

AN XY:

622820

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28476

American (AMR)

AF:

0.000251

AC:

AN:

19910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18574

East Asian (EAS)

AF:

0.00

AC:

AN:

35470

South Asian (SAS)

AF:

0.00

AC:

AN:

58634

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44154

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3820

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1025276

Other (OTH)

AF:

0.000113

AC:

AN:

52950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

AF:

0.00000663

AC:

AN:

150918

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73706

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41060

American (AMR)

AF:

0.0000659

AC:

AN:

15186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5062

South Asian (SAS)

AF:

0.00

AC:

AN:

4762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10460

Middle Eastern (MID)

AF:

0.00

AC:

AN:

300

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67640

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000743

Hom.:

ExAC

AF:

0.0000287

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 14, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.22G>A (p.G8R) alteration is located in exon 1 (coding exon 1) of the PURG gene. This alteration results from a G to A substitution at nucleotide position 22, causing the glycine (G) at amino acid position 8 to be replaced by an arginine (R). 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

Uncertain

0.43

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

.;T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.81

T;T;T

M_CAP

Benign

0.079

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N;.

PhyloP100

6.8

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.3

N;N;.

REVEL

Benign

0.075

Sift

Pathogenic

0.0

D;D;.

Sift4G

Uncertain

0.0040

D;D;.

Polyphen

0.0010

B;B;.

Vest4

0.40

MutPred

0.27

Gain of methylation at G8 (P = 0.0024);Gain of methylation at G8 (P = 0.0024);Gain of methylation at G8 (P = 0.0024);

MVP

0.043

MPC

1.0

ClinPred

0.27

GERP RS

3.4

Varity_R

0.31

gMVP

0.32

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over