Genetic Variant PURA:p.Gly48_Gly49del (chr5-140114310-TGGCGGC-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005859.5(PURA):c.141_146delCGGCGG(p.Gly48_Gly49del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,290,974 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G47G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000087 ( 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: 3.31

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: Benign. The variant received -12 ACMG points.

BP6

Variant 5-140114310-TGGCGGC-T is Benign according to our data. Variant chr5-140114310-TGGCGGC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 624066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PURA	NM_005859.5 link	c.141_146delCGGCGG	p.Gly48_Gly49del	disruptive_inframe_deletion	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.141_146delCGGCGG	p.Gly48_Gly49del	disruptive_inframe_deletion	Exon 1 of 1	6	NM_005859.5	ENSP00000332706.3		Q00577

Frequencies

GnomAD3 genomes

AF:

0.0000215

AC:

AN:

139488

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:

0.000228

Gnomad FIN

AF:

0.000113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000158

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

29190

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000868

AC:

AN:

1151486

Hom.:

AF XY:

0.0000107

AC XY:

AN XY:

558764

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24018

American (AMR)

AF:

0.00

AC:

AN:

10644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16794

East Asian (EAS)

AF:

0.00

AC:

AN:

28132

South Asian (SAS)

AF:

0.0000608

AC:

AN:

32890

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24432

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3626

European-Non Finnish (NFE)

AF:

0.00000829

AC:

AN:

964454

Other (OTH)

AF:

0.00

AC:

AN:

46496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.0000215

AC:

AN:

139488

Hom.:

Cov.:

AF XY:

0.0000148

AC XY:

AN XY:

67752

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

37470

American (AMR)

AF:

0.00

AC:

AN:

14332

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3298

East Asian (EAS)

AF:

0.00

AC:

AN:

4738

South Asian (SAS)

AF:

0.000228

AC:

AN:

4380

European-Finnish (FIN)

AF:

0.000113

AC:

AN:

8874

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.0000158

AC:

AN:

63356

Other (OTH)

AF:

0.00

AC:

AN:

1908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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

Nov 12, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Has not been previously published as pathogenic or benign to our knowledge; In-frame deletion of 2 amino acids in a repetitive region with no known function -

Sep 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PURA: BP3 -

PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome

Benign:1

Oct 03, 2023

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

3.3

Mutation Taster

=164/36

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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