5-140114310-TGGCGGCGGC-TGGCGGC

Variant names:

• chr5-140114310-TGGC-T
• rs754074166
• NM_005859.5:c.144_146delCGG

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_005859.5(PURA):​c.144_146delCGG​(p.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 0.00132 in 1,116,734 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PURA NM_005859.5 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.67

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 Benign. Variant got -12 ACMG points.

• BP6: Variant 5-140114310-TGGC-T is Benign according to our data. Variant chr5-140114310-TGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 1131105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-140114310-TGGC-T is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAdExome4 at 1479 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PURA	NM_005859.5	c.144_146delCGG	p.Gly49del	disruptive_inframe_deletion	Exon 1 of 1	ENST00000331327.5	NP_005850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PURA	ENST00000331327.5	c.144_146delCGG	p.Gly49del	disruptive_inframe_deletion	Exon 1 of 1	6	NM_005859.5	ENSP00000332706.3
PURA	ENST00000651386.1	c.144_146delCGG	p.Gly49del	disruptive_inframe_deletion	Exon 2 of 2			ENSP00000499133.1
PURA	ENST00000505703.2	c.144_146delCGG	p.Gly49del	disruptive_inframe_deletion	Exon 2 of 2	3		ENSP00000498560.1
PURA	ENST00000502351.1	c.*51_*53delGGC		downstream_gene_variant		2		ENSP00000498760.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2 AN: 139466 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.0000534

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00132 AC: 1479 AN: 1116734 Hom.: 0 AF XY: 0.00152 AC XY: 824 AN XY: 541234

Gnomad4 AFR exome AF: 0.000903

Gnomad4 AMR exome AF: 0.00411

Gnomad4 ASJ exome AF: 0.00340

Gnomad4 EAS exome AF: 0.00137

Gnomad4 SAS exome AF: 0.00672

Gnomad4 FIN exome AF: 0.00343

Gnomad4 NFE exome AF: 0.000998

Gnomad4 OTH exome AF: 0.00193

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000143 AC: 2 AN: 139552 Hom.: 0 Cov.: 32 AF XY: 0.0000147 AC XY: 1 AN XY: 67834

Gnomad4 AFR AF: 0.0000532

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: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Oct 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

Mar 26, 2018

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1

Apr 09, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PURA-related disorder Benign:1

Dec 16, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs754074166; hg19: chr5-139493895;