Variant rs1046152089 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_005859.5(PURA):c.40G>A(p.Ala14Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000192 in 1,039,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000011 ( 0 hom. )

Consequence

PURA
NM_005859.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22

Variant links:

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]

PURA links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PURA. . Gene score misZ 3.3704 (greater than the threshold 3.09). Trascript score misZ 4.4395 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 40, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome due to a point mutation, complex neurodevelopmental disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.18423292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PURA	NM_005859.5 linkuse as main transcript	c.40G>A	p.Ala14Thr	missense_variant	1/1	ENST00000331327.5	NP_005850.1	Q00577

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PURA	ENST00000331327.5 linkuse as main transcript	c.40G>A	p.Ala14Thr	missense_variant	1/1	6	NM_005859.5	ENSP00000332706.3	Q00577
PURA	ENST00000651386.1 linkuse as main transcript	c.40G>A	p.Ala14Thr	missense_variant	2/2			ENSP00000499133.1	Q00577
PURA	ENST00000505703.2 linkuse as main transcript	c.40G>A	p.Ala14Thr	missense_variant	2/2	3		ENSP00000498560.1	A0A494C0H6
PURA	ENST00000502351.1 linkuse as main transcript	c.40G>A	p.Ala14Thr	missense_variant	2/2	2		ENSP00000498760.1	A0A494C0X8

Frequencies

GnomAD3 genomes

AF:

0.00000671

AC:

AN:

148946

Hom.:

Cov.:

show subpopulations

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000112

AC:

AN:

890248

Hom.:

Cov.:

AF XY:

0.00000234

AC XY:

AN XY:

427472

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000132

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000671

AC:

AN:

148946

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72642

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.78

M_CAP

Pathogenic

0.90

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.77

MutationAssessor

Benign

-0.34

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.27

REVEL

Benign

0.10

Sift

Benign

0.062

Sift4G

Benign

0.075

Polyphen

0.0

Vest4

0.14

MutPred

0.20

Gain of glycosylation at A14 (P = 0.0286);

MVP

0.46

MPC

1.6

ClinPred

0.40

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.076

gMVP

0.24

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over