Variant chr21-33517572-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000819.5(GART):c.1739C>A(p.Pro580His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GART
NM_000819.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.88

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3671131).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GART	NM_000819.5 linkuse as main transcript	c.1739C>A	p.Pro580His	missense_variant	15/22	ENST00000381815.9	NP_000810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GART	ENST00000381815.9 linkuse as main transcript	c.1739C>A	p.Pro580His	missense_variant	15/22	1	NM_000819.5	ENSP00000371236	P1	P22102-1
GART	ENST00000381831.7 linkuse as main transcript	c.1739C>A	p.Pro580His	missense_variant	15/22	1		ENSP00000371253	P1	P22102-1
GART	ENST00000381839.7 linkuse as main transcript	c.1739C>A	p.Pro580His	missense_variant	15/22	1		ENSP00000371261	P1	P22102-1
GART	ENST00000424203.5 linkuse as main transcript	c.*822C>A		3_prime_UTR_variant, NMD_transcript_variant	15/22	1		ENSP00000390003

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251334

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.1739C>A (p.P580H) alteration is located in exon 15 (coding exon 14) of the GART gene. This alteration results from a C to A substitution at nucleotide position 1739, causing the proline (P) at amino acid position 580 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T;T

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

.;.;D

M_CAP

Benign

0.045

MetaRNN

Benign

0.37

T;T;T

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.6

M;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-4.5

D;D;D

REVEL

Benign

0.26

Sift

Benign

0.036

D;D;D

Sift4G

Uncertain

0.040

D;D;D

Polyphen

0.97

D;D;D

Vest4

0.44

MutPred

0.29

Loss of catalytic residue at P579 (P = 0.016);Loss of catalytic residue at P579 (P = 0.016);Loss of catalytic residue at P579 (P = 0.016);

MVP

0.75

MPC

0.46

ClinPred

0.97

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.50

gMVP

0.62

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over