GeneBe

5-140113537-CGCATGAGAGGGGGTGGCCGTGACTCGGTGTCCCCTCTTTGCAGGGGGCTCTGCTGCGCCGCGCAGGCCCCTCCTCCTACATCCTCTTTGGGGGGTCACTGGAAAGCAGAGCTTAGGCCCACTCTCTGTGCTTAGTATGGCAGACTCCTTCTCACCCCTAGTCCCCTAACTCCCCAGGCCGAGGCCGCCTAGGGTCTGCCCAACAGCGACAGCCACGGTGGTGGTGGTGGTGGTGGTGGTGGTAGCAGTGGTGGCGGCAGCAGCGGCAGCAGCAGCTGCGACGCTGCGCGTCCTGCTCCCTCTCCCCCACCCAGCCAGGGTTGTAGGGTGAGGGCCGGTGGGTGGGCGCCGCCTGGCGGGCGGGCGGACGGGGGGCTGGCAGCGGGGAGGGGGCGCAGGTCACGTGCCGGCGGGCGGGTGGGCGCGTACAGTAGGGCGCCCTGCTACTGTACTGGGGAGTCAGTGCCCTGTTACCGGGTCTCGTCTGTCTCGTCTCTCCCGCAGATCTCGCGAGAGTGGCTGACTGGCTGTGGGGGTTGCGGCGGCAGCAGGCGGAGCCGGGGAGGGAAAGCAGCGGCGGCTGAGGCGACTGAGGCGGCGGGCGGAGCGGCAGGCGGCGGCGGCGCGGCAGCGGAGCGCAGCATCATGGCGGACCGAGACAGCGGCAGCGAGCAGGGTGGTGCGGCGCTGGGTTCGGGCGGCTCCCTGGGGCACCCCGGCTCGGGCTCAGGCTCCGGCGGGGGCGGTGGTGGCGGCGGGGGCGGCGGCGGCAGTGGCGGCGGCGGCGGCGGGGCCCCAGGGGGGCTGCAGCACGAGACGCAGGAGCTGGCCTCCAAGCGGGTGGACATCCAGAACAAGCGCTTCTACCTGGACGTGAAGCAGAACGCCAAGGGCCGCTTCCTGAAGAT-GAGGTGGG

Position:

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The 5-140113537-CGCATGAGAGGGGGTGGCCGTGACTCGGTGTCCCCTCTTTGCAGGGGGCTCTGCTGCGCCGCGCAGGCCCCTCCTCCTACATCCTCTTTGGGGGGTCACTGGAAAGCAGAGCTTAGGCCCACTCTCTGTGCTTAGTATGGCAGACTCCTTCTCACCCCTAGTCCCCTAACTCCCCAGGCCGAGGCCGCCTAGGGTCTGCCCAACAGCGACAGCCACGGTGGTGGTGGTGGTGGTGGTGGTGGTAGCAGTGGTGGCGGCAGCAGCGGCAGCAGCAGCTGCGACGCTGCGCGTCCTGCTCCCTCTCCCCCACCCAGCCAGGGTTGTAGGGTGAGGGCCGGTGGGTGGGCGCCGCCTGGCGGGCGGGCGGACGGGGGGCTGGCAGCGGGGAGGGGGCGCAGGTCACGTGCCGGCGGGCGGGTGGGCGCGTACAGTAGGGCGCCCTGCTACTGTACTGGGGAGTCAGTGCCCTGTTACCGGGTCTCGTCTGTCTCGTCTCTCCCGCAGATCTCGCGAGAGTGGCTGACTGGCTGTGGGGGTTGCGGCGGCAGCAGGCGGAGCCGGGGAGGGAAAGCAGCGGCGGCTGAGGCGACTGAGGCGGCGGGCGGAGCGGCAGGCGGCGGCGGCGCGGCAGCGGAGCGCAGCATCATGGCGGACCGAGACAGCGGCAGCGAGCAGGGTGGTGCGGCGCTGGGTTCGGGCGGCTCCCTGGGGCACCCCGGCTCGGGCTCAGGCTCCGGCGGGGGCGGTGGTGGCGGCGGGGGCGGCGGCGGCAGTGGCGGCGGCGGCGGCGGGGCCCCAGGGGGGCTGCAGCACGAGACGCAGGAGCTGGCCTCCAAGCGGGTGGACATCCAGAACAAGCGCTTCTACCTGGACGTGAAGCAGAACGCCAAGGGCCGCTTCCTGAAGAT-GAGGTGGG variant causes a coding sequence, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PURA
NM_005859.5 coding_sequence, 5_prime_UTR

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 2.55
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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 5-140113537-CGCATGAGAGGGGGTGGCCGTGACTCGGTGTCCCCTCTTTGCAGGGGGCTCTGCTGCGCCGCGCAGGCCCCTCCTCCTACATCCTCTTTGGGGGGTCACTGGAAAGCAGAGCTTAGGCCCACTCTCTGTGCTTAGTATGGCAGACTCCTTCTCACCCCTAGTCCCCTAACTCCCCAGGCCGAGGCCGCCTAGGGTCTGCCCAACAGCGACAGCCACGGTGGTGGTGGTGGTGGTGGTGGTGGTAGCAGTGGTGGCGGCAGCAGCGGCAGCAGCAGCTGCGACGCTGCGCGTCCTGCTCCCTCTCCCCCACCCAGCCAGGGTTGTAGGGTGAGGGCCGGTGGGTGGGCGCCGCCTGGCGGGCGGGCGGACGGGGGGCTGGCAGCGGGGAGGGGGCGCAGGTCACGTGCCGGCGGGCGGGTGGGCGCGTACAGTAGGGCGCCCTGCTACTGTACTGGGGAGTCAGTGCCCTGTTACCGGGTCTCGTCTGTCTCGTCTCTCCCGCAGATCTCGCGAGAGTGGCTGACTGGCTGTGGGGGTTGCGGCGGCAGCAGGCGGAGCCGGGGAGGGAAAGCAGCGGCGGCTGAGGCGACTGAGGCGGCGGGCGGAGCGGCAGGCGGCGGCGGCGCGGCAGCGGAGCGCAGCATCATGGCGGACCGAGACAGCGGCAGCGAGCAGGGTGGTGCGGCGCTGGGTTCGGGCGGCTCCCTGGGGCACCCCGGCTCGGGCTCAGGCTCCGGCGGGGGCGGTGGTGGCGGCGGGGGCGGCGGCGGCAGTGGCGGCGGCGGCGGCGGGGCCCCAGGGGGGCTGCAGCACGAGACGCAGGAGCTGGCCTCCAAGCGGGTGGACATCCAGAACAAGCGCTTCTACCTGGACGTGAAGCAGAACGCCAAGGGCCGCTTCCTGAAGAT-GAGGTGGG is Pathogenic according to our data. Variant chr5-140113537-CGCATGAGAGGGGGTGGCCGTGACTCGGTGTCCCCTCTTTGCAGGGGGCTCTGCTGCGCCGCGCAGGCCCCTCCTCCTACATCCTCTTTGGGGGGTCACTGGAAAGCAGAGCTTAGGCCCACTCTCTGTGCTTAGTATGGCAGACTCCTTCTCACCCCTAGTCCCCTAACTCCCCAGGCCGAGGCCGCCTAGGGTCTGCCCAACAGCGACAGCCACGGTGGTGGTGGTGGTGGTGGTGGTGGTAGCAGTGGTGGCGGCAGCAGCGGCAGCAGCAGCTGCGACGCTGCGCGTCCTGCTCCCTCTCCCCCACCCAGCCAGGGTTGTAGGGTGAGGGCCGGTGGGTGGGCGCCGCCTGGCGGGCGGGCGGACGGGGGGCTGGCAGCGGGGAGGGGGCGCAGGTCACGTGCCGGCGGGCGGGTGGGCGCGTACAGTAGGGCGCCCTGCTACTGTACTGGGGAGTCAGTGCCCTGTTACCGGGTCTCGTCTGTCTCGTCTCTCCCGCAGATCTCGCGAGAGTGGCTGACTGGCTGTGGGGGTTGCGGCGGCAGCAGGCGGAGCCGGGGAGGGAAAGCAGCGGCGGCTGAGGCGACTGAGGCGGCGGGCGGAGCGGCAGGCGGCGGCGGCGCGGCAGCGGAGCGCAGCATCATGGCGGACCGAGACAGCGGCAGCGAGCAGGGTGGTGCGGCGCTGGGTTCGGGCGGCTCCCTGGGGCACCCCGGCTCGGGCTCAGGCTCCGGCGGGGGCGGTGGTGGCGGCGGGGGCGGCGGCGGCAGTGGCGGCGGCGGCGGCGGGGCCCCAGGGGGGCTGCAGCACGAGACGCAGGAGCTGGCCTCCAAGCGGGTGGACATCCAGAACAAGCGCTTCTACCTGGACGTGAAGCAGAACGCCAAGGGCCGCTTCCTGAAGAT-GAGGTGGG is described in ClinVar as [Pathogenic]. Clinvar id is 2861228.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 transcript coding_sequence_variant, 5_prime_UTR_variant 1/1 ENST00000331327.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PURAENST00000331327.5 linkuse as main transcript coding_sequence_variant, 5_prime_UTR_variant 1/1 NM_005859.5 P1
PURAENST00000502351.1 linkuse as main transcript splice_acceptor_variant, coding_sequence_variant, 5_prime_UTR_variant, 3_prime_UTR_variant, intron_variant 2/22
PURAENST00000505703.2 linkuse as main transcriptc.-141-504_263delinsGAGGTGGG splice_acceptor_variant, coding_sequence_variant, 5_prime_UTR_variant, intron_variant 2/23
PURAENST00000651386.1 linkuse as main transcriptc.-141-504_263delinsGAGGTGGG splice_acceptor_variant, coding_sequence_variant, 5_prime_UTR_variant, intron_variant 2/2 P1

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMay 04, 2023For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PURA-related conditions. This variant results in the deletion of part of exon 1 (c.-645_263delinsGAGGTGGG) of the PURA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PURA are known to be pathogenic (PMID: 29097605). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-139493122; API