chr8-31032715-G-C

Variant names:

• chr8-31032715-G-C
• rs1479221599
• NM_001323311.2:c.68C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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. 13/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.50
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17605433).
• BS2: High AC in GnomAdExome4 at 12 AD gene.

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.68C>G	p.Ser23Cys	missense	Exon 2 of 2	NP_001310240.1	Q9UJV8-1
	PURG	NM_013357.2		c.68C>G	p.Ser23Cys	missense	Exon 1 of 1	NP_037489.1	Q9UJV8-1
	PURG	NM_001015508.3		c.68C>G	p.Ser23Cys	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.68C>G	p.Ser23Cys	missense	Exon 2 of 2	ENSP00000466881.2	Q9UJV8-1
	PURG	ENST00000339382.3	TSL:1	c.68C>G	p.Ser23Cys	missense	Exon 1 of 2	ENSP00000345168.2	Q9UJV8-2
	PURG	ENST00000475541.2	TSL:6	c.68C>G	p.Ser23Cys	missense	Exon 1 of 1	ENSP00000418721.1	Q9UJV8-1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152016 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

GnomAD4 exome AF: 0.00000895 AC: 12 AN: 1341402 Hom.: 0 Cov.: 31 AF XY: 0.00000916 AC XY: 6 AN XY: 654736

African (AFR) AF: 0.00 AC: 0 AN: 29828

American (AMR) AF: 0.00 AC: 0 AN: 25446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19440

East Asian (EAS) AF: 0.00 AC: 0 AN: 38052

South Asian (SAS) AF: 0.00 AC: 0 AN: 66726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4542

European-Non Finnish (NFE) AF: 0.0000114 AC: 12 AN: 1054368

Other (OTH) AF: 0.00 AC: 0 AN: 55076

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152016 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74246

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

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2082

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions as Germline

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	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.028
Eigen_PC	Benign	0.099
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.69	N
PhyloP100		5.5
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.11
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.032	D
Polyphen		0.48	P
Vest4		0.32
MutPred		0.32		Loss of glycosylation at S23 (P = 0.0035)
MVP		0.082
MPC		0.83
ClinPred		0.52	D
GERP RS		4.2
Varity_R		0.14
gMVP		0.29
Mutation Taster		=67/33	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: rs1479221599; hg19: chr8-30890231;