4-56401240-C-T

Variant summary

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

The NM_002703.5(PPAT):c.886+90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 1,220,488 control chromosomes in the GnomAD database, including 91,962 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 0.31 (8519 hom., cov: 32)
  • Exomes 𝑓: 0.39 (83443 hom.)
• Consequence: PPAT NM_002703.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461

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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPAT	NM_002703.5	c.886+90G>A		intron_variant		ENST00000264220.6
PPAT	NR_156493.2	n.941+90G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPAT	ENST00000264220.6	c.886+90G>A		intron_variant		1	NM_002703.5	P1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47184 AN: 151896 Hom.: 8520 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.0684

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.305

GnomAD4 exome AF: 0.387 AC: 413506 AN: 1068474 Hom.: 83443 AF XY: 0.387 AC XY: 205502 AN XY: 530384

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.267

Gnomad4 ASJ exome AF: 0.412

Gnomad4 EAS exome AF: 0.0545

Gnomad4 SAS exome AF: 0.370

Gnomad4 FIN exome AF: 0.370

Gnomad4 NFE exome AF: 0.414

Gnomad4 OTH exome AF: 0.367

GnomAD4 genome AF: 0.310 AC: 47195 AN: 152014 Hom.: 8519 Cov.: 32 AF XY: 0.307 AC XY: 22845 AN XY: 74302

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.0686

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.302

Alfa AF: 0.310 Hom.: 2089

Bravo AF: 0.294

Asia WGS AF: 0.206 AC: 719 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	11
Dann	Benign	0.74

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

LitVar

Other links and lift over

dbSNP: rs956275; hg19: chr4-57267406;