chr8-31031965-C-A

Variant names:

• chr8-31031965-C-A
• NM_001323311.2:c.818G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001323311.2(PURG):​c.818G>T​(p.Arg273Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PURG NM_001323311.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.17

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PURG	NM_001323311.2	c.818G>T	p.Arg273Met	missense_variant	Exon 2 of 2	ENST00000523392.2	NP_001310240.1
PURG	NM_013357.2	c.818G>T	p.Arg273Met	missense_variant	Exon 1 of 1		NP_037489.1
PURG	NM_001015508.3	c.818G>T	p.Arg273Met	missense_variant	Exon 1 of 2		NP_001015508.1
PURG	NM_001323312.2	c.818G>T	p.Arg273Met	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.818G>T	p.Arg273Met	missense_variant	Exon 2 of 2	3	NM_001323311.2	ENSP00000466881.2
PURG	ENST00000339382.3	c.818G>T	p.Arg273Met	missense_variant	Exon 1 of 2	1		ENSP00000345168.2
PURG	ENST00000475541.2	c.818G>T	p.Arg273Met	missense_variant	Exon 1 of 1	6		ENSP00000418721.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461858 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	29
DANN	Benign	0.96
DEOGEN2	Uncertain	0.59	.;D
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.045	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.4	N;N
REVEL	Uncertain	0.39
Sift	Benign	0.035	D;D
Sift4G	Uncertain	0.043	D;D
Polyphen		1.0	D;D
Vest4		0.82
MutPred		0.70		Loss of methylation at K272 (P = 0.0266);Loss of methylation at K272 (P = 0.0266);
MVP		0.29
MPC		2.1
ClinPred		0.87	D
GERP RS		5.3
Varity_R		0.25
gMVP		0.80

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-30889481;