5-140114210-A-T

Variant names:

• chr5-140114210-A-T
• NM_005859.5:c.29A>T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Moderate BP6_Moderate

The NM_005859.5(PURA):​c.29A>T​(p.Gln10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PURA NM_005859.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.73

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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=0.1843425).
• BP6: Variant 5-140114210-A-T is Benign according to our data. Variant chr5-140114210-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2844991.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PURA	NM_005859.5	c.29A>T	p.Gln10Leu	missense_variant	Exon 1 of 1	ENST00000331327.5	NP_005850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PURA	ENST00000331327.5	c.29A>T	p.Gln10Leu	missense_variant	Exon 1 of 1	6	NM_005859.5	ENSP00000332706.3
PURA	ENST00000651386.1	c.29A>T	p.Gln10Leu	missense_variant	Exon 2 of 2			ENSP00000499133.1
PURA	ENST00000505703.2	c.29A>T	p.Gln10Leu	missense_variant	Exon 2 of 2	3		ENSP00000498560.1
PURA	ENST00000502351.1	c.29A>T	p.Gln10Leu	missense_variant	Exon 2 of 2	2		ENSP00000498760.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 10

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome Benign:1

Oct 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.39	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.67	T
M_CAP	Pathogenic	0.87	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.34	N
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.23
Sift	Benign	0.12	T
Sift4G	Benign	0.28	T
Polyphen		0.043	B
Vest4		0.25
MutPred		0.12		Loss of solvent accessibility (P = 0.0217);
MVP		0.60
MPC		1.6
ClinPred		0.30	T
GERP RS		2.3
Varity_R		0.087
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-139493795;