Variant rs2409496 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000819.5(GART):c.529G>C(p.Glu177Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000145 in 1,588,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

GART
NM_000819.5 missense, splice_region

Scores

Splicing: ADA: 0.9999

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.15

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GART	NM_000819.5 linkuse as main transcript	c.529G>C	p.Glu177Gln	missense_variant, splice_region_variant	6/22	ENST00000381815.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GART	ENST00000381815.9 linkuse as main transcript	c.529G>C	p.Glu177Gln	missense_variant, splice_region_variant	6/22	1	NM_000819.5	P1	P22102-1

Frequencies

GnomAD3 genomes

AF:

0.0000332

AC:

AN:

150660

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000194

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000222

AC:

AN:

225434

Hom.:

AF XY:

0.0000326

AC XY:

AN XY:

122678

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000156

Gnomad NFE exome

AF:

0.0000188

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000125

AC:

AN:

1438156

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

715128

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.000136

Gnomad4 NFE exome

AF:

0.00000724

Gnomad4 OTH exome

AF:

0.0000337

GnomAD4 genome

AF:

0.0000332

AC:

AN:

150660

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

73484

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000194

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.59

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T;T;.;.;.

Eigen

Benign

0.060

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.029

MetaRNN

Benign

0.20

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L;L;L;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.96

N;N;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.084

T;T;T;T;T;T

Sift4G

Benign

0.12

T;T;T;T;T;.

Polyphen

0.0030

B;B;B;.;.;.

Vest4

0.12

MutPred

0.43

Loss of disorder (P = 0.1411);Loss of disorder (P = 0.1411);Loss of disorder (P = 0.1411);Loss of disorder (P = 0.1411);Loss of disorder (P = 0.1411);Loss of disorder (P = 0.1411);

MVP

0.73

MPC

0.11

ClinPred

0.15

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.79

SpliceAI score (max)

0.72

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.72

Position offset: -3

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