Genetic Variant NM_005859.5:c.126_146dupCAGTGGCGGCGGCGGCGGCGG (chr5-140114295-G-GGGCGGCGGCGGCAGTGGCGGC) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_005859.5(PURA):c.126_146dupCAGTGGCGGCGGCGGCGGCGG(p.Gly49_Ala50insSerGlyGlyGlyGlyGlyGly) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000201 in 149,126 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. G49G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000095 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PURA
NM_005859.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.43

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 5-140114295-G-GGGCGGCGGCGGCAGTGGCGGC is Benign according to our data. Variant chr5-140114295-G-GGGCGGCGGCGGCAGTGGCGGC is described in ClinVar as [Likely_benign]. Clinvar id is 639596.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PURA	NM_005859.5 link	c.126_146dupCAGTGGCGGCGGCGGCGGCGG	p.Gly49_Ala50insSerGlyGlyGlyGlyGlyGly	disruptive_inframe_insertion	Exon 1 of 1	ENST00000331327.5	NP_005850.1	Q00577

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PURA	ENST00000331327.5 link	c.126_146dupCAGTGGCGGCGGCGGCGGCGG	p.Gly49_Ala50insSerGlyGlyGlyGlyGlyGly	disruptive_inframe_insertion	Exon 1 of 1	6	NM_005859.5	ENSP00000332706.3	Q00577
PURA	ENST00000651386.1 link	c.126_146dupCAGTGGCGGCGGCGGCGGCGG	p.Gly49_Ala50insSerGlyGlyGlyGlyGlyGly	disruptive_inframe_insertion	Exon 2 of 2			ENSP00000499133.1	Q00577
PURA	ENST00000505703.2 link	c.126_146dupCAGTGGCGGCGGCGGCGGCGG	p.Gly49_Ala50insSerGlyGlyGlyGlyGlyGly	disruptive_inframe_insertion	Exon 2 of 2	3		ENSP00000498560.1	A0A494C0H6
PURA	ENST00000502351.1 link	c.35_36insGGCGGCGGCGGCAGTGGCGGC		downstream_gene_variant		2		ENSP00000498760.1	A0A494C0X8

Frequencies

GnomAD3 genomes

AF:

0.0000201

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:

0.0000449

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000950

AC:

105

AN:

1105424

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

531428

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000108

Gnomad4 OTH exome

AF:

0.0000678

GnomAD4 genome

AF:

0.0000201

AC:

AN:

149126

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72718

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000449

Gnomad4 OTH

AF:

0.00

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

Apr 25, 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

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