8-31032715-G-A

Variant names:

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

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.68C>T​(p.Ser23Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S23C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PURG NM_001323311.2 missense
• Clinical Significance: Not reported in ClinVar
• 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: 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=0.20921227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PURG	NM_001323311.2	c.68C>T	p.Ser23Phe	missense_variant	Exon 2 of 2	ENST00000523392.2	NP_001310240.1
PURG	NM_013357.2	c.68C>T	p.Ser23Phe	missense_variant	Exon 1 of 1		NP_037489.1
PURG	NM_001015508.3	c.68C>T	p.Ser23Phe	missense_variant	Exon 1 of 2		NP_001015508.1
PURG	NM_001323312.2	c.68C>T	p.Ser23Phe	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.68C>T	p.Ser23Phe	missense_variant	Exon 2 of 2	3	NM_001323311.2	ENSP00000466881.2
PURG	ENST00000339382.3	c.68C>T	p.Ser23Phe	missense_variant	Exon 1 of 2	1		ENSP00000345168.2
PURG	ENST00000475541.2	c.68C>T	p.Ser23Phe	missense_variant	Exon 1 of 1	6		ENSP00000418721.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 132010 AF XY: 0.00

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	.;T;.
Eigen	Benign	-0.045
Eigen_PC	Benign	0.087
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N;N;.
PhyloP100		5.5
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.1	N;N;.
REVEL	Benign	0.11
Sift	Uncertain	0.0040	D;D;.
Sift4G	Uncertain	0.029	D;D;.
Polyphen		0.48	P;B;.
Vest4		0.29
MutPred		0.36		Loss of catalytic residue at S23 (P = 0.0026);Loss of catalytic residue at S23 (P = 0.0026);Loss of catalytic residue at S23 (P = 0.0026);
MVP		0.082
MPC		0.93
ClinPred		0.74	D
GERP RS		4.2
Varity_R		0.16
gMVP		0.30
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;