Variant 5-140114310-TGGCGGCGGC-TGGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
PURA	NM_005859.5 linkuse as main transcript	c.141_146delCGGCGG	p.Gly48_Gly49del	disruptive_inframe_deletion	1/1	ENST00000331327.5	NP_005850.1	Q00577

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PURA	ENST00000331327.5 linkuse as main transcript	c.141_146delCGGCGG	p.Gly48_Gly49del	disruptive_inframe_deletion	1/1	6	NM_005859.5	ENSP00000332706.3	Q00577
PURA	ENST00000651386.1 linkuse as main transcript	c.141_146delCGGCGG	p.Gly48_Gly49del	disruptive_inframe_deletion	2/2			ENSP00000499133.1	Q00577
PURA	ENST00000505703.2 linkuse as main transcript	c.141_146delCGGCGG	p.Gly48_Gly49del	disruptive_inframe_deletion	2/2	3		ENSP00000498560.1	A0A494C0H6

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

GnomAD4 exome

AF:

0.00000868

AC:

AN:

1151486

Hom.:

AF XY:

0.0000107

AC XY:

AN XY:

558764

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000608

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000829

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000215

AC:

AN:

139488

Hom.:

Cov.:

AF XY:

0.0000148

AC XY:

AN XY:

67752

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000228

Gnomad4 FIN

AF:

0.000113

Gnomad4 NFE

AF:

0.0000158

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2021	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 -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2023	PURA: BP3 -

PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 03, 2023

- -

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.

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