5-140114295-GGGCGGCGGCGGCAGTGGCGGCGGCGGC-GGGCGGCGGCGGCAGTGGCGGCGGCGGCGGCGGCAGTGGCGGCGGCGGC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_005859.5(PURA):c.126_146dup(p.Ser43_Gly49dup) variant causes a 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000095 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PURA NM_005859.5 inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.43

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]

ACMG classification

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/exons	MANE	UniProt
PURA	NM_005859.5	c.126_146dup	p.Ser43_Gly49dup	inframe_insertion	1/1	ENST00000331327.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PURA	ENST00000331327.5	c.126_146dup	p.Ser43_Gly49dup	inframe_insertion	1/1		NM_005859.5	P1
PURA	ENST00000505703.2	c.126_146dup	p.Ser43_Gly49dup	inframe_insertion	2/2	3
PURA	ENST00000651386.1	c.126_146dup	p.Ser43_Gly49dup	inframe_insertion	2/2			P1
PURA	ENST00000502351.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000201 AC: 3 AN: 149126 Hom.: 0 Cov.: 31

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.: 0 Cov.: 31 AF XY: 0.000107 AC XY: 57 AN XY: 531428

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: 3 AN: 149126 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 72718

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

Submissions by phenotype

PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Mar 26, 2022

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs750397204; hg19: chr5-139493880;