rs1350220385

Variant names:

• chr5-140114223-G-A
• rs1350220385
• NM_005859.5:c.42G>A
• PURA p.Ala14Ala

Your query was ambiguous. Multiple possible variants found:

• chr5-140114223-G-A
• chr5-140114223-G-C
• chr5-140114223-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_005859.5(PURA):​c.42G>A​(p.Ala14Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PURA NM_005859.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.390
• Publications: 0 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 5-140114223-G-A is Benign according to our data. Variant chr5-140114223-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 542080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.39 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 12 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.42G>A	p.Ala14Ala	synonymous	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.42G>A	p.Ala14Ala	synonymous	Exon 1 of 1	ENSP00000332706.3	Q00577
	PURA	ENST00000651386.1		c.42G>A	p.Ala14Ala	synonymous	Exon 2 of 2	ENSP00000499133.1	Q00577
	PURA	ENST00000505703.2	TSL:3	c.42G>A	p.Ala14Ala	synonymous	Exon 2 of 2	ENSP00000498560.1	A0A494C0H6

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149308 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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000132 AC: 12 AN: 910204 Hom.: 0 Cov.: 13 AF XY: 0.0000137 AC XY: 6 AN XY: 436706

African (AFR) AF: 0.00 AC: 0 AN: 18592

American (AMR) AF: 0.00 AC: 0 AN: 6946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11334

East Asian (EAS) AF: 0.00 AC: 0 AN: 22004

South Asian (SAS) AF: 0.00 AC: 0 AN: 16772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19784

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2588

European-Non Finnish (NFE) AF: 0.0000155 AC: 12 AN: 775878

Other (OTH) AF: 0.00 AC: 0 AN: 36306

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 149308 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 72834

African (AFR) AF: 0.00 AC: 0 AN: 40636

American (AMR) AF: 0.00 AC: 0 AN: 15026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 5070

South Asian (SAS) AF: 0.00 AC: 0 AN: 4726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67126

Other (OTH) AF: 0.00 AC: 0 AN: 2052

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	15
DANN	Benign	0.95
PhyloP100		0.39
PromoterAI		0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1350220385; hg19: chr5-139493808;