chr5-140114223-G-T

Variant names:

• chr5-140114223-G-T
• rs1350220385
• NM_005859.5:c.42G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_005859.5(PURA):​c.42G>T​(p.Ala14Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000011 in 910,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A14A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: PURA NM_005859.5 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=0.39 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PURA	NM_005859.5	MANE Select	c.42G>T	p.Ala14Ala	synonymous	Exon 1 of 1	NP_005850.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PURA	ENST00000331327.5	TSL:6 MANE Select	c.42G>T	p.Ala14Ala	synonymous	Exon 1 of 1	ENSP00000332706.3
	PURA	ENST00000651386.1		c.42G>T	p.Ala14Ala	synonymous	Exon 2 of 2	ENSP00000499133.1
	PURA	ENST00000505703.2	TSL:3	c.42G>T	p.Ala14Ala	synonymous	Exon 2 of 2	ENSP00000498560.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000110 AC: 1 AN: 910208 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 436704

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: 0.00000129 AC: 1 AN: 775882

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Benign	0.86
PhyloP100		0.39
PromoterAI		0.039	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

Other links and lift over

dbSNP: rs1350220385; hg19: chr5-139493808;