chr8-31032253-T-C

Variant names:

• chr8-31032253-T-C
• NM_001323311.2:c.530A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001323311.2(PURG):​c.530A>G​(p.Glu177Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: PURG NM_001323311.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.68
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40639523).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PURG	NM_001323311.2	c.530A>G	p.Glu177Gly	missense_variant	Exon 2 of 2	ENST00000523392.2	NP_001310240.1
PURG	NM_013357.2	c.530A>G	p.Glu177Gly	missense_variant	Exon 1 of 1		NP_037489.1
PURG	NM_001015508.3	c.530A>G	p.Glu177Gly	missense_variant	Exon 1 of 2		NP_001015508.1
PURG	NM_001323312.2	c.530A>G	p.Glu177Gly	missense_variant	Exon 2 of 3		NP_001310241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PURG	ENST00000523392.2	c.530A>G	p.Glu177Gly	missense_variant	Exon 2 of 2	3	NM_001323311.2	ENSP00000466881.2
PURG	ENST00000339382.3	c.530A>G	p.Glu177Gly	missense_variant	Exon 1 of 2	1		ENSP00000345168.2
PURG	ENST00000475541.2	c.530A>G	p.Glu177Gly	missense_variant	Exon 1 of 1	6		ENSP00000418721.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.530A>G (p.E177G) alteration is located in exon 1 (coding exon 1) of the PURG gene. This alteration results from a A to G substitution at nucleotide position 530, causing the glutamic acid (E) at amino acid position 177 to be replaced by a glycine (G). 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	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	.;T
Eigen	Benign	-0.0054
Eigen_PC	Benign	0.085
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	M;M
PhyloP100		2.7
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.17
Sift	Benign	0.41	T;T
Sift4G	Benign	0.40	T;T
Polyphen		0.45	B;B
Vest4		0.54
MutPred		0.46		Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);
MVP		0.59
MPC		2.1
ClinPred		0.69	D
GERP RS		4.1
Varity_R		0.16
gMVP		0.73
Mutation Taster		=40/60	disease causing

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

Other links and lift over

hg19: chr8-30889769;