rs2139512

Positions:

• chr4-56410453-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002703.5(PPAT):​c.129-2737C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 914,172 control chromosomes in the GnomAD database, including 207,739 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.69 (35988 hom., cov: 30)
  • Exomes 𝑓: 0.67 (171751 hom.)
• Consequence: PPAT NM_002703.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90

Genes affected

PPAT (HGNC:9238): (phosphoribosyl pyrophosphate amidotransferase) The protein encoded by this gene is a member of the purine/pyrimidine phosphoribosyltransferase family. It is a regulatory allosteric enzyme that catalyzes the first step of de novo purine nucleotide biosythetic pathway. This gene and PAICS/AIRC gene, a bifunctional enzyme catalyzing steps six and seven of this pathway, are located in close proximity on chromosome 4, and divergently transcribed from an intergenic region. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPAT	NM_002703.5	c.129-2737C>G		intron_variant		ENST00000264220.6
PPAT	NR_156493.2	n.267-2737C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPAT	ENST00000264220.6	c.129-2737C>G		intron_variant		1	NM_002703.5	P1
PPAT	ENST00000507724.1	c.129-2737C>G		intron_variant, NMD_transcript_variant		3
PPAT	ENST00000510643.5	c.129-2737C>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104316 AN: 151792 Hom.: 35952 Cov.: 30

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.674

GnomAD4 exome AF: 0.671 AC: 511471 AN: 762264 Hom.: 171751 AF XY: 0.671 AC XY: 237331 AN XY: 353842

Gnomad4 AFR exome AF: 0.687

Gnomad4 AMR exome AF: 0.772

Gnomad4 ASJ exome AF: 0.582

Gnomad4 EAS exome AF: 0.728

Gnomad4 SAS exome AF: 0.769

Gnomad4 FIN exome AF: 0.763

Gnomad4 NFE exome AF: 0.668

Gnomad4 OTH exome AF: 0.683

GnomAD4 genome AF: 0.687 AC: 104412 AN: 151908 Hom.: 35988 Cov.: 30 AF XY: 0.694 AC XY: 51525 AN XY: 74256

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.760

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.711

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.675

Alfa AF: 0.671 Hom.: 4236

Bravo AF: 0.685

Asia WGS AF: 0.738 AC: 2569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs2139512; hg19: chr4-57276619;