chr8-31032445-G-C

Variant names:

• chr8-31032445-G-C
• rs753826470
• NM_001323311.2:c.338C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001323311.2(PURG):​c.338C>G​(p.Ala113Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PURG NM_001323311.2 missense
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PURG	NM_001323311.2	c.338C>G	p.Ala113Gly	missense_variant	Exon 2 of 2	ENST00000523392.2	NP_001310240.1
PURG	NM_013357.2	c.338C>G	p.Ala113Gly	missense_variant	Exon 1 of 1		NP_037489.1
PURG	NM_001015508.3	c.338C>G	p.Ala113Gly	missense_variant	Exon 1 of 2		NP_001015508.1
PURG	NM_001323312.2	c.338C>G	p.Ala113Gly	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.338C>G	p.Ala113Gly	missense_variant	Exon 2 of 2	3	NM_001323311.2	ENSP00000466881.2
PURG	ENST00000339382.3	c.338C>G	p.Ala113Gly	missense_variant	Exon 1 of 2	1		ENSP00000345168.2
PURG	ENST00000475541.2	c.338C>G	p.Ala113Gly	missense_variant	Exon 1 of 1	6		ENSP00000418721.1

Frequencies

GnomAD3 genomes Cov.: 32

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	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	.;D;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.3	M;M;.
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-3.1	D;D;.
REVEL	Benign	0.15
Sift	Uncertain	0.0040	D;D;.
Sift4G	Benign	0.14	T;T;.
Polyphen		0.40	B;B;.
Vest4		0.40
MutPred		0.63		Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP		0.26
MPC		1.5
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.48
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.36		Position offset: 0

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;