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rs1554129135

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_ModerateBP6_Moderate

The NM_005859.5(PURA):c.920C>T(p.Ala307Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A307T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PURA
NM_005859.5 missense

Scores

4
15

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.86
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, PURA
BP4
Computational evidence support a benign effect (MetaRNN=0.15217105).
BP6
Variant 5-140115101-C-T is Benign according to our data. Variant chr5-140115101-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 475291.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PURANM_005859.5 linkuse as main transcriptc.920C>T p.Ala307Val missense_variant 1/1 ENST00000331327.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PURAENST00000331327.5 linkuse as main transcriptc.920C>T p.Ala307Val missense_variant 1/1 NM_005859.5 P1
PURAENST00000651386.1 linkuse as main transcriptc.920C>T p.Ala307Val missense_variant 2/2 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJul 28, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
Cadd
Benign
22
Dann
Uncertain
0.99
DEOGEN2
Benign
0.32
T
Eigen
Benign
-0.042
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.68
T
M_CAP
Benign
0.0095
T
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
0.98
N
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-0.21
N
REVEL
Benign
0.054
Sift
Uncertain
0.017
D
Sift4G
Benign
0.12
T
Polyphen
0.015
B
Vest4
0.35
MutPred
0.26
Gain of catalytic residue at A307 (P = 0.2535);
MVP
0.23
MPC
1.7
ClinPred
0.63
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.14
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs1554129135; hg19: chr5-139494686; API