5-140114295-GGGCGGCGGCGGCAGTGGCGGCGGCGGC-GGGC

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_005859.5(PURA):c.123_146delCGGCAGTGGCGGCGGCGGCGGCGG(p.Gly42_Gly49del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000534 in 1,254,568 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G41G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

PURA
NM_005859.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.66

Publications

0 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: Benign. The variant received -12 ACMG points.

BP6

Variant 5-140114295-GGGCGGCGGCGGCAGTGGCGGCGGC-G is Benign according to our data. Variant chr5-140114295-GGGCGGCGGCGGCAGTGGCGGCGGC-G is described in ClinVar as Likely_benign. ClinVar VariationId is 475284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PURA	NM_005859.5 link	c.123_146delCGGCAGTGGCGGCGGCGGCGGCGG	p.Gly42_Gly49del	disruptive_inframe_deletion	Exon 1 of 1	ENST00000331327.5	NP_005850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PURA	ENST00000331327.5 link	c.123_146delCGGCAGTGGCGGCGGCGGCGGCGG	p.Gly42_Gly49del	disruptive_inframe_deletion	Exon 1 of 1	6	NM_005859.5	ENSP00000332706.3

Frequencies

GnomAD3 genomes

AF:

0.0000402

AC:

AN:

149126

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000898

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000560

AC:

AN:

7138

AF XY:

0.000659

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000540

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000552

AC:

AN:

1105442

Hom.:

AF XY:

0.0000621

AC XY:

AN XY:

531434

show subpopulations

African (AFR)

AF:

0.0000882

AC:

AN:

22674

American (AMR)

AF:

0.00

AC:

AN:

8398

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13990

East Asian (EAS)

AF:

0.00

AC:

AN:

25856

South Asian (SAS)

AF:

0.000162

AC:

AN:

24734

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3174

European-Non Finnish (NFE)

AF:

0.0000574

AC:

AN:

940228

Other (OTH)

AF:

0.0000226

AC:

AN:

44282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000402

AC:

AN:

149126

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

72718

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40818

American (AMR)

AF:

0.00

AC:

AN:

15006

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3416

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000898

AC:

AN:

66838

Other (OTH)

AF:

0.00

AC:

AN:

2040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

The PURA p.Gly42_Gly49del variant was not identified in the literature but was identified in dbSNP (ID: rs1014354489) and ClinVar (classified as likely benign by Invitae). The variant was identified in control databases in 5 of 35864 chromosomes at a frequency of 0.0001394 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: South Asian in 2 of 1530 chromosomes (freq: 0.001307) and European (non-Finnish) in 3 of 18170 chromosomes (freq: 0.000165), but was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), or Other populations. This is greater than the expected frequency for the severe, early-onset autosomal dominant PURA-Related Neurodevelopmental Disorders. This variant is an in-frame deletion resulting in the removal of glycine (gly) residues from codon 42 to 49; the impact of this alteration on PURA protein function is not known however this occurs within a glycine repeat region. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. -

Dec 10, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome

Benign:1

Dec 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

5.7

Mutation Taster

=156/44

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