8-31031771-C-G

Variant names:

• chr8-31031771-C-G
• rs779485500
• NM_001323311.2:c.1012G>C

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.1012G>C​(p.Ala338Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000709 in 1,551,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. A338S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: PURG NM_001323311.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.74
• 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=0.098129004).
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PURG	NM_001323311.2	c.1012G>C	p.Ala338Pro	missense_variant	Exon 2 of 2	ENST00000523392.2	NP_001310240.1
PURG	NM_013357.2	c.1012G>C	p.Ala338Pro	missense_variant	Exon 1 of 1		NP_037489.1
PURG	NM_001015508.3	c.864+148G>C		intron_variant	Intron 1 of 1		NP_001015508.1
PURG	NM_001323312.2	c.864+148G>C		intron_variant	Intron 2 of 2		NP_001310241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PURG	ENST00000523392.2	c.1012G>C	p.Ala338Pro	missense_variant	Exon 2 of 2	3	NM_001323311.2	ENSP00000466881.2
PURG	ENST00000339382.3	c.864+148G>C		intron_variant	Intron 1 of 1	1		ENSP00000345168.2
PURG	ENST00000475541.2	c.1012G>C	p.Ala338Pro	missense_variant	Exon 1 of 1	6		ENSP00000418721.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152230 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: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000715 AC: 10 AN: 1399308 Hom.: 0 Cov.: 31 AF XY: 0.00000869 AC XY: 6 AN XY: 690214

African (AFR) AF: 0.00 AC: 0 AN: 31582

American (AMR) AF: 0.00 AC: 0 AN: 35670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25148

East Asian (EAS) AF: 0.00 AC: 0 AN: 35742

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000834 AC: 9 AN: 1078920

Other (OTH) AF: 0.00 AC: 0 AN: 58012

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74366

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.053
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
PhyloP100		5.7
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.24	N
REVEL	Benign	0.061
Sift	Benign	0.31	T
Sift4G	Benign	0.27	T
Polyphen		0.26	B
Vest4		0.13
MutPred		0.15		Gain of relative solvent accessibility (P = 0.005);
MVP		0.068
MPC		1.3
ClinPred		0.62	D
GERP RS		4.9
Varity_R		0.22
gMVP		0.32
Mutation Taster		=62/38	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: rs779485500; hg19: chr8-30889287;