Genetic Variant PPAT:n.2543T>A (chr4-56394865-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000425339.2(PPAT):n.2543T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. 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 0.45 ( 4230 hom., cov: 0)

Exomes 𝑓: 0.29 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PPAT
ENST00000425339.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.96

Publications

0 publications found

Variant links:

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]

PPAT links:

ENSG00000269921 (HGNC:58795):

ENSG00000269921 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPAT	NM_002703.5 link	c.*487T>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000264220.6	NP_002694.3
PPAT	NR_156493.2 link	n.2096T>A		non_coding_transcript_exon_variant	Exon 11 of 11

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
PPAT	ENST00000425339.2 link	n.2543T>A	non_coding_transcript_exon_variant	Exon 3 of 3	1
PPAT	ENST00000264220.6 link	c.*487T>A	3_prime_UTR_variant	Exon 11 of 11	1	NM_002703.5	ENSP00000264220.2
ENSG00000269921	ENST00000716481.1 link	n.260-1814A>T	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

33820

AN:

74968

Hom.:

4225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.556

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.547

Gnomad SAS

AF:

0.533

Gnomad FIN

AF:

0.471

Gnomad MID

AF:

0.359

Gnomad NFE

AF:

0.409

Gnomad OTH

AF:

0.439

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.286

AC:

AN:

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.286

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.451

AC:

33855

AN:

75026

Hom.:

4230

Cov.:

AF XY:

0.459

AC XY:

16978

AN XY:

37014

show subpopulations

African (AFR)

AF:

0.445

AC:

9947

AN:

22332

American (AMR)

AF:

0.557

AC:

5280

AN:

9480

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

328

AN:

1200

East Asian (EAS)

AF:

0.547

AC:

1974

AN:

3612

South Asian (SAS)

AF:

0.533

AC:

1504

AN:

2820

European-Finnish (FIN)

AF:

0.471

AC:

2025

AN:

4300

Middle Eastern (MID)

AF:

0.385

AC:

AN:

122

European-Non Finnish (NFE)

AF:

0.409

AC:

12126

AN:

29654

Other (OTH)

AF:

0.441

AC:

503

AN:

1140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

1141

2282

3422

4563

5704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

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1440

1800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.679

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.84

(source)

DANN

Benign

0.20

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over