rs578121063

Variant names:

• chr8-31033351-G-C
• rs578121063
• NM_001323311.2:c.-280C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001323311.2(PURG):​c.-280C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000728 in 156,540 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00073 (1 hom., cov: 30)
  • Exomes 𝑓: 0.00059 (0 hom.)
• Consequence: PURG NM_001323311.2 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.177
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS2: High AC in GnomAd4 at 111 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.-280C>G		5_prime_UTR	Exon 1 of 2	NP_001310240.1	Q9UJV8-1
	PURG	NM_001015508.3		c.-569C>G		5_prime_UTR	Exon 1 of 2	NP_001015508.1	Q9UJV8-2
	PURG	NM_001323312.2		c.-280C>G		5_prime_UTR	Exon 1 of 3	NP_001310241.1	Q9UJV8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PURG	ENST00000523392.2	TSL:3 MANE Select	c.-280C>G		5_prime_UTR	Exon 1 of 2	ENSP00000466881.2	Q9UJV8-1
	PURG	ENST00000339382.3	TSL:1	c.-569C>G		5_prime_UTR	Exon 1 of 2	ENSP00000345168.2	Q9UJV8-2
	PURG	ENST00000475541.2	TSL:6	c.-569C>G		5_prime_UTR	Exon 1 of 1	ENSP00000418721.1	Q9UJV8-1

Frequencies

GnomAD3 genomes AF: 0.000733 AC: 111 AN: 151380 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.000869

Gnomad EAS AF: 0.0178

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.000192

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000148

Gnomad OTH AF: 0.000479

GnomAD4 exome AF: 0.000594 AC: 3 AN: 5048 Hom.: 0 Cov.: 0 AF XY: 0.00101 AC XY: 3 AN XY: 2984

African (AFR) AF: 0.00 AC: 0 AN: 70

American (AMR) AF: 0.00 AC: 0 AN: 200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 82

East Asian (EAS) AF: 0.00602 AC: 1 AN: 166

South Asian (SAS) AF: 0.00 AC: 0 AN: 148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 14

European-Non Finnish (NFE) AF: 0.000278 AC: 1 AN: 3594

Other (OTH) AF: 0.00345 AC: 1 AN: 290

GnomAD4 genome AF: 0.000733 AC: 111 AN: 151492 Hom.: 1 Cov.: 30 AF XY: 0.000918 AC XY: 68 AN XY: 74042

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.0000655 AC: 1 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.000869 AC: 3 AN: 3454

East Asian (EAS) AF: 0.0179 AC: 91 AN: 5086

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4814

European-Finnish (FIN) AF: 0.000192 AC: 2 AN: 10404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000148 AC: 10 AN: 67722

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000648 Hom.: 0

Bravo AF: 0.000971

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Werner syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	15
DANN	Benign	0.89
PhyloP100		-0.18
PromoterAI		-0.032	Neutral

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: rs578121063; hg19: chr8-30890867;