5-140114310-TGGCGGCGGC-TGGCGGC

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

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. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. 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
• 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 -8 ACMG points.

• BP6: Variant 5-140114310-TGGC-T is Benign according to our data. Variant chr5-140114310-TGGC-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1131105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.144_146delCGG	p.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.144_146delCGG	p.Gly49del	disruptive_inframe_deletion	Exon 1 of 1	ENSP00000332706.3	Q00577
	PURA	ENST00000651386.1		c.144_146delCGG	p.Gly49del	disruptive_inframe_deletion	Exon 2 of 2	ENSP00000499133.1	Q00577
	PURA	ENST00000505703.2	TSL:3	c.144_146delCGG	p.Gly49del	disruptive_inframe_deletion	Exon 2 of 2	ENSP00000498560.1	A0A494C0H6

Frequencies

GnomAD3 genomes AF: 0.0000143 AC: 2 AN: 139466 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.00918 AC: 268 AN: 29190 AF XY: 0.00965

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00979

Gnomad ASJ exome AF: 0.0122

Gnomad EAS exome AF: 0.00251

Gnomad FIN exome AF: 0.0124

Gnomad NFE exome AF: 0.00860

Gnomad OTH exome AF: 0.0155

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000903 AC: 21 AN: 23248

American (AMR) AF: 0.00411 AC: 42 AN: 10220

Ashkenazi Jewish (ASJ) AF: 0.00340 AC: 55 AN: 16154

East Asian (EAS) AF: 0.00137 AC: 37 AN: 26912

South Asian (SAS) AF: 0.00672 AC: 213 AN: 31678

European-Finnish (FIN) AF: 0.00343 AC: 80 AN: 23328

Middle Eastern (MID) AF: 0.00258 AC: 9 AN: 3490

European-Non Finnish (NFE) AF: 0.000998 AC: 935 AN: 936714

Other (OTH) AF: 0.00193 AC: 87 AN: 44990

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000532 AC: 2 AN: 37570

American (AMR) AF: 0.00 AC: 0 AN: 14344

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4718

South Asian (SAS) AF: 0.00 AC: 0 AN: 4362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 63346

Other (OTH) AF: 0.00 AC: 0 AN: 1932

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)
-	-	1	PURA-related disorder (1)
-	-	1	PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs754074166; hg19: chr5-139493895; COSMIC: COSV58762879; COSMIC: COSV58762879;