Genetic Variant PURA:p.Gly49dup (chr5-140114310-T-TGGC) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_005859.5(PURA):c.144_146dupCGG(p.Gly49dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000574 in 1,291,082 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00057 ( 1 hom. )

Consequence

PURA
NM_005859.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 0.895

Variant links:

Genes affected

PURA (HGNC:9701): (purine rich element binding protein A) This gene product is a sequence-specific, single-stranded DNA-binding protein. It binds preferentially to the single strand of the purine-rich element termed PUR, which is present at origins of replication and in gene flanking regions in a variety of eukaryotes from yeasts through humans. Thus, it is implicated in the control of both DNA replication and transcription. Deletion of this gene has been associated with myelodysplastic syndrome and acute myelogenous leukemia. [provided by RefSeq, Jul 2008]

PURA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 5-140114310-T-TGGC is Benign according to our data. Variant chr5-140114310-T-TGGC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 436451.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=2, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 87 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PURA	NM_005859.5 link	c.144_146dupCGG	p.Gly49dup	disruptive_inframe_insertion	Exon 1 of 1	ENST00000331327.5	NP_005850.1	Q00577

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PURA	ENST00000331327.5 link	c.144_146dupCGG	p.Gly49dup	disruptive_inframe_insertion	Exon 1 of 1	6	NM_005859.5	ENSP00000332706.3	Q00577
PURA	ENST00000651386.1 link	c.144_146dupCGG	p.Gly49dup	disruptive_inframe_insertion	Exon 2 of 2			ENSP00000499133.1	Q00577
PURA	ENST00000505703.2 link	c.144_146dupCGG	p.Gly49dup	disruptive_inframe_insertion	Exon 2 of 2	3		ENSP00000498560.1	A0A494C0H6
PURA	ENST00000502351.1 link	c.50_51insGGC		downstream_gene_variant		2		ENSP00000498760.1	A0A494C0X8

Frequencies

GnomAD3 genomes

AF:

0.000624

AC:

AN:

139490

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000427

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000419

Gnomad ASJ

AF:

0.00485

Gnomad EAS

AF:

0.00127

Gnomad SAS

AF:

0.000457

Gnomad FIN

AF:

0.000113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000584

Gnomad OTH

AF:

0.00157

GnomAD3 exomes

AF:

0.000651

AC:

AN:

29190

Hom.:

AF XY:

0.000772

AC XY:

AN XY:

18126

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000699

Gnomad ASJ exome

AF:

0.00554

Gnomad EAS exome

AF:

0.000836

Gnomad SAS exome

AF:

0.000515

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000269

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000568

AC:

654

AN:

1151504

Hom.:

Cov.:

AF XY:

0.000600

AC XY:

335

AN XY:

558780

show subpopulations

Gnomad4 AFR exome

AF:

0.000666

Gnomad4 AMR exome

AF:

0.000376

Gnomad4 ASJ exome

AF:

0.00459

Gnomad4 EAS exome

AF:

0.000391

Gnomad4 SAS exome

AF:

0.000456

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000495

Gnomad4 OTH exome

AF:

0.000968

GnomAD4 genome

AF:

0.000623

AC:

AN:

139578

Hom.:

Cov.:

AF XY:

0.000663

AC XY:

AN XY:

67850

show subpopulations

Gnomad4 AFR

AF:

0.000426

Gnomad4 AMR

AF:

0.000418

Gnomad4 ASJ

AF:

0.00485

Gnomad4 EAS

AF:

0.00127

Gnomad4 SAS

AF:

0.000459

Gnomad4 FIN

AF:

0.000113

Gnomad4 NFE

AF:

0.000584

Gnomad4 OTH

AF:

0.00155

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 24, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PURA: BS1, BS2 -

not specified

Uncertain:1

Sep 07, 2016

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Dec 18, 2017

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

PURA-related disorder

Benign:1

Jul 27, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

5-140114310-TGGCGGCGGC-TGGCGGCGGCGGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over