chr8-31032674-A-G

Variant names:

Variant summary

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

The NM_001323311.2(PURG):c.109T>C(p.Ser37Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,374,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

PURG
NM_001323311.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.838

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: 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=0.069716424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PURG	NM_001323311.2 link	c.109T>C	p.Ser37Pro	missense_variant	Exon 2 of 2	ENST00000523392.2	NP_001310240.1	Q9UJV8-1
PURG	NM_013357.2 link	c.109T>C	p.Ser37Pro	missense_variant	Exon 1 of 1		NP_037489.1	Q9UJV8-1
PURG	NM_001015508.3 link	c.109T>C	p.Ser37Pro	missense_variant	Exon 1 of 2		NP_001015508.1	Q9UJV8-2
PURG	NM_001323312.2 link	c.109T>C	p.Ser37Pro	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.109T>C	p.Ser37Pro	missense_variant	Exon 2 of 2	3	NM_001323311.2	ENSP00000466881.2	Q9UJV8-1K7ENC1
PURG	ENST00000339382.3 link	c.109T>C	p.Ser37Pro	missense_variant	Exon 1 of 2	1		ENSP00000345168.2	Q9UJV8-2
PURG	ENST00000475541.2 link	c.109T>C	p.Ser37Pro	missense_variant	Exon 1 of 1	6		ENSP00000418721.1	Q9UJV8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000146

AC:

AN:

1374494

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

677892

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

30364

American (AMR)

AF:

0.00

AC:

AN:

36600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20452

East Asian (EAS)

AF:

0.00

AC:

AN:

36938

South Asian (SAS)

AF:

0.00

AC:

AN:

76598

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48838

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5120

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1064280

Other (OTH)

AF:

0.0000362

AC:

AN:

55304

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 07, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.109T>C (p.S37P) alteration is located in exon 1 (coding exon 1) of the PURG gene. This alteration results from a T to C substitution at nucleotide position 109, causing the serine (S) at amino acid position 37 to be replaced by a proline (P). 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

0.086

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.011

.;T;.

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.52

T;T;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.070

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;L;.

PhyloP100

0.84

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.50

N;N;.

REVEL

Benign

0.031

Sift

Benign

0.36

T;T;.

Sift4G

Benign

0.28

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.14

MutPred

0.16

Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);

MVP

0.043

MPC

1.1

ClinPred

0.053

GERP RS

2.2

Varity_R

0.10

gMVP

0.14

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr8-31032674-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over