Genetic Variant NM_005859.5:c.2T>C (chr5-140114183-T-C) – ACMG Classification: Pathogenic (14 pts)

Variant summary

Our verdict is Pathogenic. The variant received 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP5_Moderate

The NM_005859.5(PURA):c.2T>C(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PURA
NM_005859.5 start_lost

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.83

Publications

0 publications found

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:

MALINC1 (HGNC:49009): (mitosis associated long intergenic non-coding RNA 1)

MALINC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 14 ACMG points.

PVS1

Start lost variant, next in-frame start position is after 95 pathogenic variants. Next in-frame start position is after 104 codons. Genomic position: 140114491. Lost 0.320 part of the original CDS.

PS1

Another start lost variant in NM_005859.5 (PURA) was described as [Likely_pathogenic] in ClinVar

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 5-140114183-T-C is Pathogenic according to our data. Variant chr5-140114183-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 2807849.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2T>C	p.Met1?	start_lost	Exon 1 of 1	NP_005850.1	Q00577

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PURA	ENST00000331327.5	TSL:6 MANE Select	c.2T>C	p.Met1?	start_lost	Exon 1 of 1	ENSP00000332706.3	Q00577
PURA	ENST00000651386.1		c.2T>C	p.Met1?	start_lost	Exon 2 of 2	ENSP00000499133.1	Q00577
PURA	ENST00000505703.2	TSL:3	c.2T>C	p.Met1?	start_lost	Exon 2 of 2	ENSP00000498560.1	A0A494C0H6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

606046

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

295768

African (AFR)

AF:

0.00

AC:

AN:

12736

American (AMR)

AF:

0.00

AC:

AN:

6146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9098

East Asian (EAS)

AF:

0.00

AC:

AN:

19636

South Asian (SAS)

AF:

0.00

AC:

AN:

10930

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1952

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

501128

Other (OTH)

AF:

0.00

AC:

AN:

25862

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.39

Eigen

Benign

-0.042

Eigen_PC

Benign

-0.0042

FATHMM_MKL

Benign

0.38

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.91

MetaRNN

Pathogenic

0.98

MetaSVM

Benign

-0.89

PhyloP100

1.8

PROVEAN

Benign

-1.2

REVEL

Benign

0.24

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

0.46

Vest4

0.63

MutPred

0.97

Gain of phosphorylation at M1 (P = 0.0013)

MVP

0.47

ClinPred

0.99

GERP RS

3.2

PromoterAI

-0.81

Under-expression

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.81

gMVP

0.53

Mutation Taster

=8/192

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over