5-140114310-TGGCGGCGGC-TGGC

Variant names:

• chr5-140114310-TGGCGGC-T
• rs754074166
• NM_005859.5:c.141_146delCGGCGG

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

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 (★★). Synonymous variant affecting the same amino acid position (i.e. G47G) has been classified 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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.31
• Publications: 1 publications found

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]

MALINC1 (HGNC:49009): (mitosis associated long intergenic non-coding RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 624066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005859.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PURA	NM_005859.5	MANE Select	c.141_146delCGGCGG	p.Gly48_Gly49del	disruptive_inframe_deletion	Exon 1 of 1	NP_005850.1	Q00577

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PURA	ENST00000331327.5	TSL:6 MANE Select	c.141_146delCGGCGG	p.Gly48_Gly49del	disruptive_inframe_deletion	Exon 1 of 1	ENSP00000332706.3	Q00577
	PURA	ENST00000651386.1		c.141_146delCGGCGG	p.Gly48_Gly49del	disruptive_inframe_deletion	Exon 2 of 2	ENSP00000499133.1	Q00577
	PURA	ENST00000505703.2	TSL:3	c.141_146delCGGCGG	p.Gly48_Gly49del	disruptive_inframe_deletion	Exon 2 of 2	ENSP00000498560.1	A0A494C0H6

Frequencies

GnomAD3 genomes AF: 0.0000215 AC: 3 AN: 139488 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.00 AC: 0 AN: 29190 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000868 AC: 10 AN: 1151486 Hom.: 0 AF XY: 0.0000107 AC XY: 6 AN XY: 558764

African (AFR) AF: 0.00 AC: 0 AN: 24018

American (AMR) AF: 0.00 AC: 0 AN: 10644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16794

East Asian (EAS) AF: 0.00 AC: 0 AN: 28132

South Asian (SAS) AF: 0.0000608 AC: 2 AN: 32890

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3626

European-Non Finnish (NFE) AF: 0.00000829 AC: 8 AN: 964454

Other (OTH) AF: 0.00 AC: 0 AN: 46496

GnomAD4 genome AF: 0.0000215 AC: 3 AN: 139488 Hom.: 0 Cov.: 32 AF XY: 0.0000148 AC XY: 1 AN XY: 67752

African (AFR) AF: 0.00 AC: 0 AN: 37470

American (AMR) AF: 0.00 AC: 0 AN: 14332

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3298

East Asian (EAS) AF: 0.00 AC: 0 AN: 4738

South Asian (SAS) AF: 0.000228 AC: 1 AN: 4380

European-Finnish (FIN) AF: 0.000113 AC: 1 AN: 8874

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.0000158 AC: 1 AN: 63356

Other (OTH) AF: 0.00 AC: 0 AN: 1908

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.3
Mutation Taster		=164/36	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs754074166; hg19: chr5-139493895;