Variant 8-31032715-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001323311.2(PURG):c.68C>G(p.Ser23Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000937 in 1,493,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

PURG
NM_001323311.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.50

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17605433).

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PURG	NM_001323311.2 linkuse as main transcript	c.68C>G	p.Ser23Cys	missense_variant	2/2	ENST00000523392.2
PURG	NM_013357.2 linkuse as main transcript	c.68C>G	p.Ser23Cys	missense_variant	1/1
PURG	NM_001015508.3 linkuse as main transcript	c.68C>G	p.Ser23Cys	missense_variant	1/2
PURG	NM_001323312.2 linkuse as main transcript	c.68C>G	p.Ser23Cys	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PURG	ENST00000523392.2 linkuse as main transcript	c.68C>G	p.Ser23Cys	missense_variant	2/2	3	NM_001323311.2	P1	Q9UJV8-1
PURG	ENST00000339382.3 linkuse as main transcript	c.68C>G	p.Ser23Cys	missense_variant	1/2	1			Q9UJV8-2
PURG	ENST00000475541.2 linkuse as main transcript	c.68C>G	p.Ser23Cys	missense_variant	1/1			P1	Q9UJV8-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000895

AC:

AN:

1341402

Hom.:

Cov.:

AF XY:

0.00000916

AC XY:

AN XY:

654736

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000114

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152016

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.68C>G (p.S23C) alteration is located in exon 1 (coding exon 1) of the PURG gene. This alteration results from a C to G substitution at nucleotide position 68, causing the serine (S) at amino acid position 23 to be replaced by a cysteine (C). 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

0.11

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Benign

0.96

Eigen

Benign

-0.028

Eigen_PC

Benign

0.099

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.69

N;N;.

MutationTaster

Benign

0.91

N;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.99

N;N;.

REVEL

Benign

0.11

Sift

Uncertain

0.010

D;D;.

Sift4G

Uncertain

0.032

D;D;.

Polyphen

0.48

P;B;.

Vest4

0.32

MutPred

0.32

Loss of glycosylation at S23 (P = 0.0035);Loss of glycosylation at S23 (P = 0.0035);Loss of glycosylation at S23 (P = 0.0035);

MVP

0.082

MPC

0.83

ClinPred

0.52

GERP RS

4.2

Varity_R

0.14

gMVP

0.29

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over