8-31031773-T-C

Position:

• chr8-31031773-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001323311.2(PURG):​c.1010A>G​(p.Lys337Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PURG NM_001323311.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.502

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028015912).
• BP6: Variant 8-31031773-T-C is Benign according to our data. Variant chr8-31031773-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2569497.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PURG	NM_001323311.2	c.1010A>G	p.Lys337Arg	missense_variant	2/2	ENST00000523392.2
PURG	NM_013357.2	c.1010A>G	p.Lys337Arg	missense_variant	1/1
PURG	NM_001015508.3	c.864+146A>G		intron_variant
PURG	NM_001323312.2	c.864+146A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PURG	ENST00000523392.2	c.1010A>G	p.Lys337Arg	missense_variant	2/2	3	NM_001323311.2	P1
PURG	ENST00000339382.3	c.864+146A>G		intron_variant		1
PURG	ENST00000475541.2	c.1010A>G	p.Lys337Arg	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	17
DANN	Benign	0.81
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.1	N
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.055
Sift	Benign	0.82	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.010
MutPred		0.20		Loss of ubiquitination at K337 (P = 3e-04);
MVP		0.068
MPC		0.70
ClinPred		0.030	T
GERP RS		3.8
Varity_R		0.039
gMVP		0.18

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: chr8-30889289;