5-140114224-C-G

Variant names:

• chr5-140114224-C-G
• rs923665124
• NM_005859.5:c.43C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005859.5(PURA):​c.43C>G​(p.Leu15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,069,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L15P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: PURA NM_005859.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.474
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14842495).

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.43C>G	p.Leu15Val	missense	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.43C>G	p.Leu15Val	missense	Exon 1 of 1	ENSP00000332706.3	Q00577
	PURA	ENST00000651386.1		c.43C>G	p.Leu15Val	missense	Exon 2 of 2	ENSP00000499133.1	Q00577
	PURA	ENST00000505703.2	TSL:3	c.43C>G	p.Leu15Val	missense	Exon 2 of 2	ENSP00000498560.1	A0A494C0H6

Frequencies

GnomAD3 genomes AF: 0.00000677 AC: 1 AN: 147640 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000251

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: 0.00000108 AC: 1 AN: 921800 Hom.: 0 Cov.: 13 AF XY: 0.00000226 AC XY: 1 AN XY: 442042

African (AFR) AF: 0.0000532 AC: 1 AN: 18806

American (AMR) AF: 0.00 AC: 0 AN: 6922

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11390

East Asian (EAS) AF: 0.00 AC: 0 AN: 21998

South Asian (SAS) AF: 0.00 AC: 0 AN: 17000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2592

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 786824

Other (OTH) AF: 0.00 AC: 0 AN: 36638

GnomAD4 genome AF: 0.00000677 AC: 1 AN: 147640 Hom.: 0 Cov.: 31 AF XY: 0.0000139 AC XY: 1 AN XY: 71926

African (AFR) AF: 0.0000251 AC: 1 AN: 39898

American (AMR) AF: 0.00 AC: 0 AN: 14912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3434

East Asian (EAS) AF: 0.00 AC: 0 AN: 5006

South Asian (SAS) AF: 0.00 AC: 0 AN: 4642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9744

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66756

Other (OTH) AF: 0.00 AC: 0 AN: 2044

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.51	T
M_CAP	Pathogenic	0.86	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.47
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.020	N
REVEL	Benign	0.16
Sift	Benign	0.034	D
Sift4G	Benign	0.49	T
Polyphen		0.0030	B
Vest4		0.087
MutPred		0.20		Gain of sheet (P = 0.0149)
MVP		0.31
MPC		1.7
ClinPred		0.043	T
GERP RS		2.6
PromoterAI		-0.0070	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.12
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs923665124; hg19: chr5-139493809;