5-140114221-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_ModerateBP6_Very_StrongBS2

The NM_005859.5(PURA):c.40G>C(p.Ala14Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,039,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

PURA
NM_005859.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PP2

Missense variant in the PURA gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 44 curated pathogenic missense variants (we use a threshold of 10). The gene has 19 curated benign missense variants. Gene score misZ: 3.3704 (above the threshold of 3.09). Trascript score misZ: 4.4395 (above the threshold of 3.09). GenCC associations: The gene is linked to 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=0.2178011).

BP6

Variant 5-140114221-G-C is Benign according to our data. Variant chr5-140114221-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 570676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PURA	NM_005859.5 link	c.40G>C	p.Ala14Pro	missense_variant	Exon 1 of 1	ENST00000331327.5	NP_005850.1	Q00577

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PURA	ENST00000331327.5 link	c.40G>C	p.Ala14Pro	missense_variant	Exon 1 of 1	6	NM_005859.5	ENSP00000332706.3	Q00577
PURA	ENST00000651386.1 link	c.40G>C	p.Ala14Pro	missense_variant	Exon 2 of 2			ENSP00000499133.1	Q00577
PURA	ENST00000505703.2 link	c.40G>C	p.Ala14Pro	missense_variant	Exon 2 of 2	3		ENSP00000498560.1	A0A494C0H6
PURA	ENST00000502351.1 link	c.40G>C	p.Ala14Pro	missense_variant	Exon 2 of 2	2		ENSP00000498760.1	A0A494C0X8

Frequencies

GnomAD3 genomes

AF:

0.000148

AC:

AN:

148946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000543

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:

0.00000562

AC:

AN:

890248

Hom.:

Cov.:

AF XY:

0.00000468

AC XY:

AN XY:

427472

show subpopulations

Gnomad4 AFR exome

AF:

0.000220

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:

0.00

Gnomad4 OTH exome

AF:

0.0000280

GnomAD4 genome

AF:

0.000148

AC:

AN:

149058

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

AN XY:

72762

show subpopulations

Gnomad4 AFR

AF:

0.000542

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000196

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome

Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Jun 12, 2018

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.36

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.70

M_CAP

Pathogenic

0.92

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.66

MutationAssessor

Benign

-0.34

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.37

REVEL

Benign

0.20

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.012

Polyphen

0.13

Vest4

0.24

MutPred

0.24

Gain of loop (P = 0.0166);

MVP

0.55

MPC

2.1

ClinPred

0.55

GERP RS

2.6

Varity_R

0.19

gMVP

0.44

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over