Variant 21-33524806-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000819.5(GART):c.1261G>A(p.Val421Ile) variant causes a missense change. The variant allele was found at a frequency of 0.785 in 1,614,086 control chromosomes in the GnomAD database, including 500,004 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.82 ( 51808 hom., cov: 33)

Exomes 𝑓: 0.78 ( 448196 hom. )

Consequence

GART
NM_000819.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.77

Variant links:

Genes affected

GART (HGNC:4163): (phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase) The protein encoded by this gene is a trifunctional polypeptide. It has phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase activity which is required for de novo purine biosynthesis. This enzyme is highly conserved in vertebrates. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

GART links:

GART (HGNC:):

GART links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.5641482E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GART	NM_000819.5 linkuse as main transcript	c.1261G>A	p.Val421Ile	missense_variant	11/22	ENST00000381815.9	NP_000810.1	P22102-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GART	ENST00000381815.9 linkuse as main transcript	c.1261G>A	p.Val421Ile	missense_variant	11/22	1	NM_000819.5	ENSP00000371236.4		P22102-1

Frequencies

GnomAD3 genomes

AF:

0.822

AC:

125072

AN:

152138

Hom.:

51754

Cov.:

show subpopulations

Gnomad AFR

AF:

0.900

Gnomad AMI

AF:

0.714

Gnomad AMR

AF:

0.859

Gnomad ASJ

AF:

0.710

Gnomad EAS

AF:

0.983

Gnomad SAS

AF:

0.785

Gnomad FIN

AF:

0.830

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.764

Gnomad OTH

AF:

0.797

GnomAD3 exomes

AF:

0.812

AC:

204156

AN:

251440

Hom.:

83749

AF XY:

0.803

AC XY:

109108

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.904

Gnomad AMR exome

AF:

0.896

Gnomad ASJ exome

AF:

0.708

Gnomad EAS exome

AF:

0.993

Gnomad SAS exome

AF:

0.774

Gnomad FIN exome

AF:

0.831

Gnomad NFE exome

AF:

0.761

Gnomad OTH exome

AF:

0.790

GnomAD4 exome

AF:

0.781

AC:

1142198

AN:

1461828

Hom.:

448196

Cov.:

AF XY:

0.779

AC XY:

566721

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.905

Gnomad4 AMR exome

AF:

0.890

Gnomad4 ASJ exome

AF:

0.715

Gnomad4 EAS exome

AF:

0.976

Gnomad4 SAS exome

AF:

0.772

Gnomad4 FIN exome

AF:

0.822

Gnomad4 NFE exome

AF:

0.766

Gnomad4 OTH exome

AF:

0.793

GnomAD4 genome

AF:

0.822

AC:

125185

AN:

152258

Hom.:

51808

Cov.:

AF XY:

0.827

AC XY:

61586

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.900

Gnomad4 AMR

AF:

0.859

Gnomad4 ASJ

AF:

0.710

Gnomad4 EAS

AF:

0.983

Gnomad4 SAS

AF:

0.783

Gnomad4 FIN

AF:

0.830

Gnomad4 NFE

AF:

0.764

Gnomad4 OTH

AF:

0.799

Alfa

AF:

0.779

Hom.:

83723

Bravo

AF:

0.832

TwinsUK

AF:

0.772

AC:

2861

ALSPAC

AF:

0.761

AC:

2933

ESP6500AA

AF:

0.902

AC:

3973

ESP6500EA

AF:

0.761

AC:

6541

ExAC

AF:

0.808

AC:

98085

Asia WGS

AF:

0.911

AC:

3169

AN:

3478

EpiCase

AF:

0.751

EpiControl

AF:

0.749

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.14

DEOGEN2

Benign

0.049

T;T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.64

.;.;T;T

MetaRNN

Benign

0.0000026

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-3.8

N;N;N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

0.92

N;N;N;N

REVEL

Benign

0.14

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;B;B;.

Vest4

0.054

MPC

0.081

ClinPred

0.0068

GERP RS

6.0

Varity_R

0.036

gMVP

0.79

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over