NM_005859.5:c.144_146dupCGG

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -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). Synonymous variant affecting the same amino acid position (i.e. G49G) has been classified as Likely benign.

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

Publications

1 publications found

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:

MALINC1 (HGNC:49009): (mitosis associated long intergenic non-coding RNA 1)

MALINC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 436451.

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	Appris	UniProt
PURA	ENST00000331327.5 link	c.144_146dupCGG	p.Gly49dup	disruptive_inframe_insertion	Exon 1 of 1	6	NM_005859.5	ENSP00000332706.3		Q00577

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

GnomAD2 exomes

AF:

0.000651

AC:

AN:

29190

AF XY:

0.000772

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 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

African (AFR)

AF:

0.000666

AC:

AN:

24018

American (AMR)

AF:

0.000376

AC:

AN:

10644

Ashkenazi Jewish (ASJ)

AF:

0.00459

AC:

AN:

16790

East Asian (EAS)

AF:

0.000391

AC:

AN:

28132

South Asian (SAS)

AF:

0.000456

AC:

AN:

32896

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24432

Middle Eastern (MID)

AF:

0.00248

AC:

AN:

3626

European-Non Finnish (NFE)

AF:

0.000495

AC:

477

AN:

964470

Other (OTH)

AF:

0.000968

AC:

AN:

46496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

130

162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000623

AC:

AN:

139578

Hom.:

Cov.:

AF XY:

0.000663

AC XY:

AN XY:

67850

show subpopulations

African (AFR)

AF:

0.000426

AC:

AN:

37576

American (AMR)

AF:

0.000418

AC:

AN:

14350

Ashkenazi Jewish (ASJ)

AF:

0.00485

AC:

AN:

3298

East Asian (EAS)

AF:

0.00127

AC:

AN:

4720

South Asian (SAS)

AF:

0.000459

AC:

AN:

4362

European-Finnish (FIN)

AF:

0.000113

AC:

AN:

8874

Middle Eastern (MID)

AF:

0.00

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.000584

AC:

AN:

63348

Other (OTH)

AF:

0.00155

AC:

AN:

1932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000540

Hom.:

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

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PURA: BS1, BS2 -

Apr 24, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

PhyloP100

0.90

Mutation Taster

=78/22

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over