chr5-140114608-C-A

Variant names:

• chr5-140114608-C-A
• rs1554129084
• NM_005859.5:c.427C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1 PM2

The NM_005859.5(PURA):​c.427C>A​(p.Leu143Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,160 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L143V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PURA NM_005859.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.11
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM1: In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 7 uncertain in NM_005859.5
• PM2: Very rare variant in population databases, with high coverage

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.427C>A	p.Leu143Ile	missense	Exon 1 of 1	NP_005850.1	Q00577

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PURA	ENST00000331327.5	TSL:6 MANE Select	c.427C>A	p.Leu143Ile	missense	Exon 1 of 1	ENSP00000332706.3	Q00577
	PURA	ENST00000651386.1		c.427C>A	p.Leu143Ile	missense	Exon 2 of 2	ENSP00000499133.1	Q00577
	MALINC1	ENST00000520928.2	TSL:3	n.108G>T		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455160 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 723788

African (AFR) AF: 0.00 AC: 0 AN: 33400

American (AMR) AF: 0.00 AC: 0 AN: 44324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26008

East Asian (EAS) AF: 0.00 AC: 0 AN: 39584

South Asian (SAS) AF: 0.00 AC: 0 AN: 85958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110346

Other (OTH) AF: 0.00 AC: 0 AN: 60126

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	34
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.64	D
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.1
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.16
Sift	Benign	0.13	T
Sift4G	Uncertain	0.035	D
Polyphen		0.93	P
Vest4		0.48
MutPred		0.78		Loss of stability (P = 0.0382)
MVP		0.23
MPC		2.5
ClinPred		0.97	D
GERP RS		5.0
PromoterAI		0.064	Neutral
Varity_R		0.33
gMVP		0.95
Mutation Taster		=36/64	disease causing

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

Other links and lift over

dbSNP: rs1554129084; hg19: chr5-139494193;