4-56401240-C-T

Variant names:

• chr4-56401240-C-T
• rs956275
• NM_002703.5:c.886+90G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002703.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPAT	NM_002703.5	MANE Select	c.886+90G>A		intron	N/A	NP_002694.3
	PPAT	NR_156493.2		n.941+90G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPAT	ENST00000264220.6	TSL:1 MANE Select	c.886+90G>A		intron	N/A	ENSP00000264220.2
	PPAT	ENST00000507648.5	TSL:5	n.*150G>A		downstream_gene	N/A

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

African (AFR) AF: 0.134 AC: 3160 AN: 23500

American (AMR) AF: 0.267 AC: 5642 AN: 21124

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 7422 AN: 18008

East Asian (EAS) AF: 0.0545 AC: 1889 AN: 34682

South Asian (SAS) AF: 0.370 AC: 21429 AN: 57874

European-Finnish (FIN) AF: 0.370 AC: 17262 AN: 46662

Middle Eastern (MID) AF: 0.379 AC: 1190 AN: 3136

European-Non Finnish (NFE) AF: 0.414 AC: 338558 AN: 817326

Other (OTH) AF: 0.367 AC: 16954 AN: 46162

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

African (AFR) AF: 0.145 AC: 6006 AN: 41484

American (AMR) AF: 0.301 AC: 4600 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1398 AN: 3468

East Asian (EAS) AF: 0.0686 AC: 355 AN: 5176

South Asian (SAS) AF: 0.343 AC: 1654 AN: 4820

European-Finnish (FIN) AF: 0.375 AC: 3955 AN: 10558

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28108 AN: 67936

Other (OTH) AF: 0.302 AC: 637 AN: 2110

Alfa AF: 0.330 Hom.: 3605

Bravo AF: 0.294

Asia WGS AF: 0.206 AC: 719 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.74
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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: rs956275; hg19: chr4-57267406;