8-31032445-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001323311.2(PURG):c.338C>T(p.Ala113Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: PURG NM_001323311.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.75

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3423872).
• BS2: High AC in GnomAdExome at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PURG	NM_001323311.2	c.338C>T	p.Ala113Val	missense_variant	2/2	ENST00000523392.2
PURG	NM_013357.2	c.338C>T	p.Ala113Val	missense_variant	1/1
PURG	NM_001015508.3	c.338C>T	p.Ala113Val	missense_variant	1/2
PURG	NM_001323312.2	c.338C>T	p.Ala113Val	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PURG	ENST00000523392.2	c.338C>T	p.Ala113Val	missense_variant	2/2	3	NM_001323311.2	P1
PURG	ENST00000339382.3	c.338C>T	p.Ala113Val	missense_variant	1/2	1
PURG	ENST00000475541.2	c.338C>T	p.Ala113Val	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251366 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135878

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461788 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727200

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ExAC AF: 0.0000247 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2022

The c.338C>T (p.A113V) alteration is located in exon 1 (coding exon 1) of the PURG gene. This alteration results from a C to T substitution at nucleotide position 338, causing the alanine (A) at amino acid position 113 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
Cadd	Uncertain	25
Dann	Uncertain	0.99
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.4	N;N;.
REVEL	Benign	0.15
Sift	Benign	0.47	T;T;.
Sift4G	Benign	0.23	T;T;.
Polyphen		0.88	P;P;.
Vest4		0.21
MutPred		0.65		Gain of methylation at K116 (P = 0.1704);Gain of methylation at K116 (P = 0.1704);Gain of methylation at K116 (P = 0.1704);
MVP		0.10
MPC		1.6
ClinPred		0.75	D
GERP RS		4.8
Varity_R		0.20
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs753826470; hg19: chr8-30889961;