Genetic Variant PURA:p.Ser43_Gly49del (chr5-140114295-GGGCGGCGGCGGCAGTGGCGGC-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_005859.5(PURA):c.126_146delCAGTGGCGGCGGCGGCGGCGG(p.Ser43_Gly49del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000262 in 1,105,442 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (★).

Frequency

Genomes: 𝑓 0.000047 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000026 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

PURA
NM_005859.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

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: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 5-140114295-GGGCGGCGGCGGCAGTGGCGGC-G is Benign according to our data. Variant chr5-140114295-GGGCGGCGGCGGCAGTGGCGGC-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1629684.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 29 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PURA	NM_005859.5 link	c.126_146delCAGTGGCGGCGGCGGCGGCGG	p.Ser43_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.126_146delCAGTGGCGGCGGCGGCGGCGG	p.Ser43_Gly49del	disruptive_inframe_deletion	Exon 1 of 1	6	NM_005859.5	ENSP00000332706.3		Q00577

Frequencies

GnomAD3 genomes

AF:

0.0000469

AC:

AN:

149126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000490

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000666

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000449

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000140

AC:

AN:

7138

AF XY:

0.000220

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:

0.000270

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000262

AC:

AN:

1105442

Hom.:

AF XY:

0.0000263

AC XY:

AN XY:

531432

show subpopulations

African (AFR)

AF:

0.0000441

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:

0.0000404

AC:

AN:

24732

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3174

European-Non Finnish (NFE)

AF:

0.0000255

AC:

AN:

940230

Other (OTH)

AF:

0.0000677

AC:

AN:

44282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000469

AC:

AN:

149226

Hom.:

Cov.:

AF XY:

0.0000549

AC XY:

AN XY:

72828

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000489

AC:

AN:

40932

American (AMR)

AF:

0.0000666

AC:

AN:

15026

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3416

East Asian (EAS)

AF:

0.00

AC:

AN:

5120

South Asian (SAS)

AF:

0.000211

AC:

AN:

4748

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000449

AC:

AN:

66828

Other (OTH)

AF:

0.00

AC:

AN:

2062

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000255179), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.368

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:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome

Benign:1

Oct 28, 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

5.7

Mutation Taster

=167/33

polymorphism

(source)

Splicing

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

Publications

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5-140114295-GGGCGGCGGCGGCAGTGGCGGCGGCGGC-GGGCGGC

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