8-31032172-C-T

Variant names:

• chr8-31032172-C-T
• rs1311927652
• NM_001323311.2:c.611G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001323311.2(PURG):​c.611G>A​(p.Arg204Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: PURG NM_001323311.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.72
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PURG	NM_001323311.2	c.611G>A	p.Arg204Gln	missense_variant	Exon 2 of 2	ENST00000523392.2	NP_001310240.1
PURG	NM_013357.2	c.611G>A	p.Arg204Gln	missense_variant	Exon 1 of 1		NP_037489.1
PURG	NM_001015508.3	c.611G>A	p.Arg204Gln	missense_variant	Exon 1 of 2		NP_001015508.1
PURG	NM_001323312.2	c.611G>A	p.Arg204Gln	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.611G>A	p.Arg204Gln	missense_variant	Exon 2 of 2	3	NM_001323311.2	ENSP00000466881.2
PURG	ENST00000339382.3	c.611G>A	p.Arg204Gln	missense_variant	Exon 1 of 2	1		ENSP00000345168.2
PURG	ENST00000475541.2	c.611G>A	p.Arg204Gln	missense_variant	Exon 1 of 1	6		ENSP00000418721.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152152 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251494 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 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: 86254

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74328

African (AFR) AF: 0.00 AC: 0 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000414 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 01, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.611G>A (p.R204Q) 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 611, causing the arginine (R) at amino acid position 204 to be replaced by a glutamine (Q). 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	0.29
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.45	.;T
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.2	M;M
PhyloP100		2.7
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.27
Sift	Benign	0.079	T;T
Sift4G	Benign	0.083	T;T
Polyphen		1.0	D;D
Vest4		0.47
MutPred		0.73		Loss of methylation at R204 (P = 0.0089);Loss of methylation at R204 (P = 0.0089);
MVP		0.42
MPC		2.1
ClinPred		0.63	D
GERP RS		5.3
Varity_R		0.32
gMVP		0.55
Mutation Taster		=53/47	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

Other links and lift over

dbSNP: rs1311927652; hg19: chr8-30889688;