NM_001323311.2:c.755G>A

Variant names:

• chr8-31032028-C-T
• NM_001323311.2:c.755G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001323311.2(PURG):​c.755G>A​(p.Arg252Lys) 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. 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)
• Consequence: PURG NM_001323311.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.10
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1940003).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323311.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PURG	NM_001323311.2	MANE Select	c.755G>A	p.Arg252Lys	missense	Exon 2 of 2	NP_001310240.1	Q9UJV8-1
	PURG	NM_013357.2		c.755G>A	p.Arg252Lys	missense	Exon 1 of 1	NP_037489.1	Q9UJV8-1
	PURG	NM_001015508.3		c.755G>A	p.Arg252Lys	missense	Exon 1 of 2	NP_001015508.1	Q9UJV8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PURG	ENST00000523392.2	TSL:3 MANE Select	c.755G>A	p.Arg252Lys	missense	Exon 2 of 2	ENSP00000466881.2	Q9UJV8-1
	PURG	ENST00000339382.3	TSL:1	c.755G>A	p.Arg252Lys	missense	Exon 1 of 2	ENSP00000345168.2	Q9UJV8-2
	PURG	ENST00000475541.2	TSL:6	c.755G>A	p.Arg252Lys	missense	Exon 1 of 1	ENSP00000418721.1	Q9UJV8-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.053
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.1
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.096
Sift	Benign	0.28	T
Sift4G	Benign	0.35	T
Polyphen		0.57	P
Vest4		0.24
MutPred		0.46		Gain of ubiquitination at R252 (P = 0.0029)
MVP		0.27
MPC		1.2
ClinPred		0.47	T
GERP RS		5.3
Varity_R		0.18
gMVP		0.70
Mutation Taster		=62/38	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

hg19: chr8-30889544;